Biomedical subjects

H H Samson

Publications and source records attributed to H H Samson.

At least 37 records · Page 2Linked to original sources

PubMed1999

Blood ethanol concentrations in rats drinking sucrose/ethanol solutions.

BACKGROUND: The addition of sucrose to ethanol solutions results in a substantial increase in ethanol self-administration by rats that are deprived of neither food nor water. However, if sucrose alters ethanol absorption or metabolism, resulting in blood ethanol concentrations (BECs) not different from those resulting from lower intakes of ethanol/water solutions, then the usefulness of sucrose/ethanol mixtures in increasing ethanol consumption is questionable. The present study was conducted to determine whether the addition of sucrose to ethanol solutions altered BECs in an operant self-administration paradigm. METHODS: Tail blood (from male Long-Evans rats) was collected 30 min after the intake of four different solutions, i.e., 5% sucrose/20% ethanol, 5% sucrose/10% ethanol, 2% sucrose/10% ethanol, and 10% ethanol. RESULTS: Ethanol intakes (mean, 1.57+/-0.21 g/kg) and BECs (mean, 78.4+/-9.3 mg/100 ml) were highest when 5% sucrose was added to the ethanol solution. Moreover, the ratios between ethanol intakes and resulting BECs were approximately the same for all solutions. CONCLUSIONS: These findings indicate that, under the conditions of this procedure, the BEC reached is dependent on the amount of ethanol consumed and is not influenced by the addition of sucrose to the solution.

Alcohol Drinking↗

PubMed1999

Breakpoint determination and ethanol self-administration using an across-session progressive ratio procedure in the rat.

BACKGROUND: Progressive ratio schedules are used to determine the "breakpoint" or limit to the amount of "work" that a subject is willing to perform to obtain a reinforcer. Reinforcing efficacy is inferred from the breakpoint values, which are typically measured in a single session by increasing the number of responses required for successive reinforcer presentations. This procedure is not feasible, however, when assessing the reinforcing efficacy of a substance that can change as a function of its physiological actions during self-administration, as in the case of ethanol. METHODS: The present study made use of a procedure that increased the response requirement across single daily sessions rather than within a session. Completion of the response requirement in each daily session resulted in the presentation of a drinking tube that allowed for self-administration of ethanol for a 20-min period. This procedure made possible the assessment of ethanol-directed appetitive (number of lever presses) and consummatory (number of licks and intake volume) behaviors. Reliable responding for 10% ethanol was initiated using sucrose-substitution on a fixed ratio (FR) 4 schedule in male Long Evans rats. Then four successive breakpoint determinations were made which were separated by a return to the FR4 schedule to re-establish baseline responding. RESULTS: The results indicated that there was an increase in breakpoint values from the first to the second determination, which was then stable over the following three determinations. Individual rats reached breakpoints as high as 240 lever presses to receive access to 10% ethanol and maintained ethanol intake over sessions in the 1.0 g/kg range. Ethanol intake (g/kg), however, was stable across all four determinations (mean 0.86 +/- 0.06 to 1.01 +/- 0.10). Moreover, ethanol intake was not related to the preceding appetitive responding, as no differences between intake on the session before a breakpoint (high FR) and the following baseline period (FR4) were observed. CONCLUSIONS: This model provides an assessment of the distinct mechanisms that mediate ethanol-seeking versus ethanol consumption in subjects that drink measurable amounts of ethanol, with the appetitive behaviors not altered by the pharmacological effects of ethanol.

Alcohol Drinking↗

PubMed1998

Effects of the self-administration of ethanol and ethanol/sucrose on rates of local cerebral glucose utilization in rats.

In a previous study, the voluntary ingestion of ethanol by rats was found to be associated with a discrete pattern of changes in functional activity that included the nucleus accumbens, medial prefrontal cortex, basolateral and central nuclei of the amygdala, as well as the ventral midbrain. Rats in this study, however, consumed a combination of ethanol in a sucrose vehicle. The purpose of the present experiment was to characterize the role of sucrose in determining the effects of orally self-administered ethanol using the quantitative autoradiographic 2-[14C]deoxyglucose (2DG) method for measurement of rates of local cerebral glucose utilization. A modified sucrose-substitution procedure was employed to train three groups of Wistar rats to self-administer either water, 10% ethanol (10E), or a 10% ethanol/2% sucrose solution (10E/2S) in daily sessions. An additional group of rats was trained using a modified acclimation procedure (home cage) in order to determine if any exposure to sucrose would alter rates of glucose utilization. Once stable rates of consumption were established, the 2DG method was applied immediately following completion of the final test session. Rats received a dose of ethanol equivalent to 0.5 g kg-1 on the day of the procedure or a comparable volume of water. Rates of energy metabolism were significantly increased in all three groups of rats that consumed ethanol (10E/2S, 10E, and home cage), as compared to rates in rats that consumed water. The areas of significant change included the rostral pole and posterior shell of the nucleus accumbens, medial prefrontal cortex, the basolateral and central nuclei of the amygdala, the ventral tegmental area, and the substantia nigra pars compacta. Thus, the pattern of changes in functional brain activity that accompanies voluntary ingestion of ethanol is independent of the vehicle in which the ethanol is presented or the procedures used to initiate consumption. Furthermore, these data demonstrate that it is the simultaneous activation of an interrelated network of limbic brain regions that serves as the substrate of the effects of ethanol self-administration.

Animals↗

PubMed1998

Effects of the atypical antipsychotic remoxipride on alcohol self-administration.

Remoxipride is a dopamine (DA) D2 antagonist that produces fewer of the side effects normally associated with chronic DA antagonist administration. It has been demonstrated that DA antagonists can reduce the desire for a second drink in alcoholics. However, because of the usual side effects associated with DA antagonist administration, chronic use as an adjunct to alcoholism treatment has not been considered. Because the DA D2 antagonist haloperidol reduces ethanol self-administration in an operant animal model of ethanol self-administration, this study was designed to determine whether remoxipride would produce similar results. Six Long-Evans rats were initiated to self-administer ethanol in daily 30-min operant sessions using a sucrose-substitution procedure. Following establishment of ethanol-reinforced lever pressing, remoxipride (0.5, 1.0, 5.0, or 10.0 mg/kg) or haloperidol (0.01, 0.05, or 0.1 mg/kg) were injected 30 min prior to the sessions. Remoxipride produced an approximate 50% reduction in the number of ethanol presentations per session at the highest dose tested (10.0 mg/kg) and did so by terminating the ethanol-drinking bout earlier in the session. Haloperidol also decreased ethanol presentations with the highest dose tested (0.1 mg/kg) producing the largest effect. These data indicate that remoxipride produces reductions in ethanol-reinforced responding similar to those observed with another DA antagonist. Because remoxipride produces fewer of the side effects commonly observed with chronic DA antagonist administration, it could prove to be a useful adjunct in the treatment of excessive alcohol consumption.

Alcohol Drinking↗

PubMed1998

Exposure to sucrose-quinine solutions does not increase ethanol consumption.

The taste of ethanol can be aversive or preferred based on prior experience with ethanol consumption. A preference for ethanol's taste is thought to result from the association of ethanol's taste with its neuropharmacological activity. However, acclimation to ethanol's aversive taste may also play a role in increased ethanol consumption following prolonged exposure. The present study examined if acclimation to a bitter-sweet tastant, which has been suggested to share similar taste qualities with ethanol, would increase ethanol intake with only minimal prior experience of an association of ethanol intake with its neuropharmacological activity. Male Long-Evans rats were trained to drink 10% sucrose during 20-min sessions. The consumption of 0-20% ethanol was then determined before and after exposure to a sucrose-quinine solution. Before the sucrose-quinine taste acclimation procedure, the initial intake of sucrose-quinine was low and similar to 5% ethanol. After the acclimation procedure, increases in sucrose-quinine intake, but not ethanol intake, were observed. These data could indicate that any similarity in the taste qualities of sucrose-quinine and ethanol solutions are diminished following exposure to sucrose-quinine. Alternatively, the differential changes in sucrose-quinine and ethanol intake could be the result of being differentially regulated by a combination of taste and postingestive factors. Overall, these data indicate that exposure to sucrose-quinine, which resulted in increased intake of sucrose-quinine, was not sufficient to alter ethanol intake. Rather, exposure to taste and postingestive factors associated with ethanol may be necessary to increase ethanol intake.

Alcohol Drinking↗

PubMed1998

Metabolic mapping of the effects of oral alcohol self-administration in rats.

The functional effects of the voluntary consumption of ethanol in rats were investigated using the quantitative autoradiographic 2-[14C]deoxyglucose method for measurement of rates of local cerebral glucose utilization. A modified sucrose-substitution procedure was used to train three groups of Wistar rats to self-administer water, a 5% sucrose solution, or a 10% ethanol/5% sucrose solution in daily sessions. Once stable rates of consumption were established, the 2-[14C]deoxyglucose method was applied immediately after completion of the final test session. Rats received a dose of ethanol equivalent to 0.5 g/kg (n = 6) on the day of the procedure or a comparable volume of sucrose solution (n = 6) or water (n = 5). Rates of local cerebral glucose utilization in rats that ingested water did not differ from those that rats consumed a 5% sucrose solution. In contrast, voluntary ethanol consumption produced a highly discrete pattern of changes in rates of glucose utilization. Ethanol ingestion increased cerebral metabolism, as compared with rates of metabolism in rats that consumed either water or sucrose in the rostral pole and shell of the nucleus accumbens, medial prefrontal cortex, lateral septum, basolateral and central nuclei of the amygdala, substantia nigra, and the ventral tegmental area. This pattern of alterations in functional activity is distinctly different from that observed when equivalent doses of ethanol are administered acutely, emphasizing the importance of self-administration in determining the changes in glucose utilization. Furthermore, within the nucleus accumbens, glucose utilization was selectively augmented in the rostral pole and shell subterritories, whereas cerebral metabolism in the core was unaffected. Finally, these data demonstrate that it is the simultaneous activation of an interconnected network of limbic brain regions that serves as the substrate of the effects of voluntarily ingested ethanol.

Alcohol Drinking↗

PubMed1998

The reinforcing effects of ethanol are altered by the endogenous neurosteroid, allopregnanolone.

We examined the effect of systemic administration of the endogenously occurring progesterone metabolite, allopregnanolone, on oral self-administration of ethanol by male rats. Rats were trained to perform an operant response for presentation of 0.1 ml of a solution of 10% ethanol in water using the sucrose fading technique. After acquisition of stable lever-press responding on a fixed-ratio 4 schedule, subjects received subcutaneous injections of 1, 3, or 10 mg/kg of allopregnanolone, or vehicle, 20 min prior to the self-administration session. Pretreatment with 3 mg/kg, but not 1 or 10 mg/kg, increased the mean total number of lever press responses made to obtain ethanol, and therefore increased the mean total number of ethanol presentations. The number of responses and response rate were examined as a function of the number of "runs" within the 30-min session; a "run" was defined as a series of consecutive responses with an interresponse interval of <1 min. The increase in total responses after 3 mg/kg was due in part to an increased number of responses for the first run of the session, with no effect on response rates. However, the higher dose of 10 mg/kg decreased response rates within the first run. Thus, allopregnanolone alters ethanol-reinforced responding at concentrations lower than those that depress rates of responding. The effects of administration of the benzodiazepene, diazepam, were determined for comparison with those of the neurosteroid. The subcutaneous injection of 0.3, 1.0, or 3.0 mg/kg of diazepam did not produce any clear dose-dependent changes in measures of ethanol-reinforced operant responding, supporting the suggestion of differences in the contribution of the benzodiazepene and neurosteroid binding sites to GABA(A) receptor function. The results indicate that exogenous administration of allopregnanolone dose-dependently alters ethanol-reinforced operant responding, and suggest that this endogenously occurring neurosteroid could mediate some of the reinforcing effects of ethanol.

Alcohol Drinking↗

PubMed1998

Effects of nicotine and mecamylamine microinjections into the nucleus accumbens on ethanol and sucrose self-administration.

Nicotine (NIC) and ethanol (ETOH) are both drugs of abuse that can affect similar pathways in the central nervous system. However, the role of nicotinic processes in ETOH's reinforcing actions is unclear. Although the mesolimbic dopamine systems are known to be involved in the reinforcing effects of ETOH, the role of nicotinic receptors within the nucleus accumbens (NAc) in ETOH reinforcement has not been studied. To address this issue, adult male Long-Evans rats were initiated to self-administer ETOH (10% v/v, n = 14) using the sucrose-substitution procedure or sucrose (5% w/v, n = 8) in a 30-min operant session. They were then surgically implanted with bilateral stainless-steel guide cannulae to allow for microinjection into the core of the NAc. After recovery from surgery, presession microinjections of NIC (0.3, 3.3, 10, 30, and 60 microg/1 microl/brain) or the antagonist mecamylamine (MEC) (1, 3, 10, 30, and 60 microg/1 microl/brain) were performed prior to an ETOH or sucrose self-administration session. NIC (3.3 and 60 microg/microl) and MEC (30 microg/microl) both reduced ETOH self-administration behavior, without affecting sucrose-reinforced behavior. A reduction in the total duration of ETOH responding (termination) was also observed after either 60 microg/microl of NIC and 30 microg/microl of MEC. The lack of a clear dose-response relationship for the agonist and the antagonist indicates that the interaction between the NAc nicotinic system and ETOH self-administration is complex.

Acetylcholine↗

PubMed1998

Appetitive and consummatory behaviors in the control of ethanol consumption: a measure of ethanol seeking behavior.

Models of ethanol self-administration in animals have demonstrated that ethanol can reinforce a variety of behaviors, independent of ethanol's caloric or fluid properties. However, the processes that control self-administration remain unclear. Determining factors related to ethanol seeking behavior, independent of consumption, is central to the concepts of intake regulation. The model described in this article proposes a method to separate the initial appetitive (seeking) behavior from the following consummatory (drinking) behavior to assess each behavior type. Rats were trained to lever press to gain access to a drinking tube connected to a fluid bottle containing either 10% ethanol or 3% sucrose for 20 min. When the response requirement to obtain access to the tube was increased, it was found that both solutions supported the same amount of responding (breakpoint was at approximately a fixed ratio 32 requirement), indicating equal reinforcer strength. However, regardless of the response requirement, if access to the fluids occurred, intakes were not changed. This suggests that factors besides those of reinforcer efficacy are important in controlling the size of the consummatory bout. Based on these findings, we believe that this model will be useful in determining factors related to seeking behaviors and the control of drinking bout size.

Alcohol Drinking↗

PubMed1998

Comparison of alcohol-preferring and nonpreferring selectively bred rat lines. I. Ethanol initiation and limited access operant self-administration.

Several lines of alcohol-preferring and alcohol-nonpreferring rats have been developed using selective breeding based on 24-hr homecage ethanol consumption. However, it remains unclear if the selection based on two-bottle choice resulted in similar ethanol self-administration when measured using an operant procedure. In this paper, we compare our previous work using alcohol-accepting (AA) and alcohol-nonaccepting (ANA) rats with data obtained using the identical procedures in the (P) and (NP) rat lines, and both replicate lines of the high alcohol drinking (HAD1 and HAD2) and low alcohol drinking (LAD1 and LAD2) lines. All rats from each line were initiated to self-administer 10% ethanol using the sucrose fading procedure. After initiation, increasing concentrations of ethanol up to 30% ethanol were tested. The results indicated that only in the LAD1 and LAD2 lines was ethanol presentation not able to maintain lever pressing after initiation. Compared with the AA line, the P, HAD1, HAD2, and NP lines all self-administered more ethanol in the operant paradigm after initiation. The ANA line self-administered less ethanol than the AA line, but more than the LAD lines. Correlational analysis of homecage consumption with operant ethanol self-administration suggested that approximately 62% of the genetic variance in operant self-administration resulted from genes selected for the homecage drinking. At the same time, it was clear that there were genetic influences on operant self-administration that were not selected for by homecage ethanol drinking.

Alcohol Drinking↗

PubMed1998

Comparison of alcohol-preferring and nonpreferring selectively bred rat lines. II. Operant self-administration in a continuous-access situation.

Several rat lines have been developed using preference/nonpreference and daily ethanol intake in the homecage as criteria for selective breeding. Using these lines, behavioral and neural factors that may underlie the genetic basis for the control of ethanol consumption have been examined. In this paper, we report data from eight of these selected lines: the Alcohol-Preferring (P) and Alcohol-Nonpreferring (NP), the Alcohol-Accepting (AA) and Alcohol-Nonaccepting (ANA), and the High Alcohol Drinking (HAD1 and HAD2) and Low Alcohol Drinking (LAD1 and LAD2) rats. All lines were tested using operant procedures and the same protocols for both the ethanol self-administration initiation and measurement of continuous-access ethanol consumption. During continuous access, the animals were housed in operant chambers with access to 10% (v/v) ethanol after responses on one lever, food pellets (45 mg) after responses on a second lever, and water in a drinking tube that was connected to a drinkometer circuit. Under these procedures, both similarities and differences among the selected lines on continuous-access operant ethanol intake were observed. For example, overall total homecage ethanol drinking was similar for the AA and both HAD lines. When examined in the operant continuous-access situation, however, the AA rats displayed a different consumption pattem, compared with the HAD lines. Data suggest that the frequency of drinking bouts was a primary factor in the phenotypic homecage selection of the preferring lines that was revealed by the use of the continuous-access operant procedure. In general, data suggest that genes related to ethanol preference and intake in homecage continuous-access situations may not be identical to those related to ethanol's reinforcing function in operant continuous-access conditions. Because ethanol consumption appears to be controlled by different drinking patterns across lines, the selected lines provide for a variety of models to understand how varying genotypes can impact ethanol consumption.

Alcohol Drinking↗

PubMed1997

Intranucleus accumbens amphetamine infusions enhance responding maintained by a stimulus complex paired with oral ethanol self-administration.

Six male Long-Evans rats were trained to self-administer 10% ethanol (v/v) during 30 min operant sessions. A licking response on an empty drinking tube resulted in the presentation of reinforcement from an automatic dipper. During the initiation of ethanol self-administration, a tone-light stimulus complex was paired with all ethanol presentations. When 10% ethanol maintained responding, guide cannulae aimed at the nucleus accumbens (NAcc) were implanted into the brain. The ability of the paired stimulus complex to reinforce a new operant response (i.e., a lever press) was then examined. To test for the development of the new response, responding on one lever resulted in presentation of only the paired tone-light stimulus complex (contingency-associated lever) while responding on an alternate lever had no programmed consequences (no contingency-associated lever). Prior to some new response sessions, amphetamine (5-20 microg/microl) was infused into the NAcc to examine the influence of dopamine on responding maintained by the stimulus complex. Ethanol intake during the sessions prior to new response testing averaged 0.49 +/- 0.07 g/g. During new response sessions no significant differences in lever pressure during no-drug conditions (control, sham, injection or vehicle injection) were observed between the contingency-associated and no contingency-associated levers. Intra-NAcc infusion of amphetamine (5-20 microg/microl) resulted in significant increases in lever pressing only on the contingency-associated lever. These data suggest that increasing NAcc dopamine levels with amphetamine enhanced the ability of the stimulus complex to function as a reinforcer. Further studies examining the ability of potentially more salient stimuli (i.e., taste of ethanol) to function as conditioned reinforcers associated with ethanol self-administration are warranted due to the apparent inability of the paired tone-light stimulus complex to function as a reinforcer without amphetamine-induced activation of the NAcc.

Animals↗

PubMed1997

Alcohol self-administration: further examination of the role of dopamine receptors in the nucleus accumbens.

One of the functions of the mesolimbic dopamine (DA) system is to regulate the process of reinforcement, a process that is thought to influence drug self-administration. This study tested the effects of centrally administered DA receptor ligands on ethanol self-administration behavior. Long-Evans rats were trained to lever press on a fixed-ratio 4 schedule of ethanol (10% v/v) reinforcement. DA agonists and antagonists were then bilaterally microinjected (0.5 microliter/side) into the nucleus accumbens (N Acc) 10-min before sessions to test for effects on the onset, maintenance, and termination of ethanol self-administration. Infusions of the D1-like agonist SKF 38393 (0.03 to 3.0 micrograms) produced no effect on ethanol self-administration. The D1-like antagonist SCH 23390 (0.5 to 2.0 micrograms) reduced total responding by decreasing the time course of self-administration without altering response rate. The D2-like agonist quinpirole produced a biphasic effect on self-administration. Quinpirole (1.0 microgram) increased total responses and response rate, whereas higher doses (4.0 to 10.0 micrograms) decreased total responding as a result of early termination. The D2-like antagonist raclopride (0.1 to 1.0 microgram) reduced total responding by decreasing time course and response rate. Co-administration of either SKF 38393 or SCH 23390 with quinpirole prevented the behavioral effects observed with the low doses of quinpirole. Thus, in the N Acc either increased activation of D1-like receptors or their blockade can affect the expression of the behavioral effects of the D2-like agonist. This suggests that some intermediate level of D1 activation is required to observe the D2 effect. The decreases in total responding produced by raclopride were enhanced by co-administration of SKF 38393, but not altered by SCH 23390, thus suggesting that D1-like and D2-like receptors in the N Acc interact in the regulation of ethanol self-administration in a manner similar to their interactive regulation of other behaviors.

Alcohol Drinking↗

PubMed1997

Differential changes in sucrose/ethanol and sucrose maintained responding by independently altering ethanol or sucrose concentration.

Increased reinforcing efficacy of sucrose/ethanol solutions in comparison to sucrose solutions has been previously demonstrated. However, the contribution of the components of the sucrose/ethanol solution is not well defined. The present study used a multiple schedule of reinforcement to evaluate the differential changes in reinforcer presentations as sucrose or ethanol concentrations were altered. Male Long-Evans rats were trained to press a lever on a multiple fixed ratio 4-fixed ratio 4 schedule which was composed of alternating 2-min components. During one component, 5% sucrose/10% ethanol was presented as the reinforcer and, in the second component, 5% sucrose was presented. Independent manipulations of the ethanol concentration (0, 5, and 20%) in the sucrose/ethanol solution or sucrose concentration (0, 10, and 20%) in the sucrose solution were then performed. Increasing the ethanol concentration in the sucrose/ethanol solution resulted in decreases in reinforcer delivery but increases in ethanol intake (grams per kilogram) and total session caloric intake. Increasing the sucrose concentration in the sucrose solution resulted in significant increases in sucrose reinforcer delivery and total session caloric intake. During the concentration manipulations, the number of reinforcers presented of the unchanged reinforcer was not affected. Differential changes in the pattern of reinforcer presentation after ethanol and sucrose concentration manipulations during successive access periods suggest that sucrose and sucrose/ethanol maintained responding are differentially regulated. Changes in sucrose maintained responding after increases in the sucrose concentration were observed early in the session suggesting a strong influence of taste in regulating intake. Changes in sucrose/ethanol maintained responding after increases in the ethanol concentration occurred later in the session and suggest that postingestive effects (i.e., pharmacology) play a major role in the regulation of sucrose/ethanol intake. In addition, the differential patterns of sucrose/ethanol and sucrose maintained behavior suggest that the ethanol component of the sucrose/ethanol solution plays an important role in maintaining sucrose/ethanol reinforced behavior.

Alcohol Drinking↗

PubMed1997

Ethanol-reinforced responding by AA and ANA rats following the sucrose-substitution initiation procedure.

Ethanol-reinforced responding was initiated in male AA and ANA rats using the sucrose-substitution procedure. Before the initiation procedure, a homecage, two-bottle preference test was conducted. The rats were then trained to respond on an Fixed-Ratio 1 schedule with sucrose reinforcement. Over sessions, ethanol was added gradually to the sucrose solution as the concentration of sucrose was reduced until 10% ethanol (v/v) alone functioned as the reinforcer for lever pressing. The schedule of reinforcement was then increased to Fixed-Ratio 4. Next, the ethanol concentration presented as the reinforcer was increased over weeks to 15%, 20%, 30%, and then returned to 10%. A second homecage test was then performed. The results showed that the AA and ANA lines differed significantly on preference and intake (g/kg) during the homecage preference tests. There was a significant increase in preference during the second homecage test. During sucrose substitution, initial large differences in responding were observed between the lines. When the ethanol concentration was increased, intake (grams per kilogram) increased for the AA line but not for the ANA line. These effects were a function of no change in responding by the AA rats as concentration was increased and a decrease in responding by the ANA rats at the higher concentrations (20% and 30%). Taken together, data indicate that ethanol can function as a positive reinforcer for the behavior of AA and ANA rats. Even though 10% ethanol functioned as a reinforcer similarly for the two lines, ethanol intake in the AA line was significantly greater at the higher concentrations of ethanol, suggesting that ethanol functioned as a qualitatively different reinforcer for the AA rats, compared with the ANA rats.

Alcohol Drinking↗

PubMed1997

Changes in oral ethanol self-administration patterns resulting from ethanol concentration manipulations.

A variety of initiation procedures have been used to develop oral ethanol consumption. Using the sucrose-substitution procedure, oral self-administration of ethanol-water solutions with ethanol concentrations as high as 40% can be initiated in food- and fluid-sated rats. An important question for these models is the relationship between ethanol concentration and self-administration patterns after initiation. This study examined the differential patterns of ethanol self-administration maintained by a range of ethanol solutions (10 to 30%) over a 5-week period, compared with rats maintained on 10% ethanol for 5 weeks. In 43 male Long Evans rats, the sucrose-substitution procedure was used to initiate responding maintained by 10% ethanol on a Fixed Ratio 4 schedule of reinforcement. The ethanol concentration presented was then increased to 30% in stepwise fashion and then returned to 10% [Ethanol Concentration Manipulation (ECM) group, n = 32], or 10% ethanol was maintained as the reinforcer for 5 weeks [Control (Con) group, n = 11]. Significant increases in ethanol intake and decreases in responding were associated with increased ethanol concentration. Although no overall differences in total session responding were observed in either group between week 1 and week 5 (10E vs. 10E), examination of changes in initial low responders of the ECM group revealed significant increases in responding that were not observed in the initial low responders of the Con group. Significant increases in momentary response rates were observed on both the ECM and Con groups, independent of the ethanol concentration presented. Increases in response rate in the ECM group were the result of increases in initial low rate and high rate responders; however, the increased response rates in the Con group were the result of increases only in the initial low rate responders. These data suggest that the ECM procedure can aid in the initiation of ethanol self-administration and may be particularly useful in rats of heterogeneous stock.

Alcohol Drinking↗

PubMed1996

Effects of ventral tegmental microinjections of the GABAA agonist muscimol on self-administration of ethanol and sucrose.

Two groups of Long-Evans rats were trained to lever press on a fixed-ratio 4 (FR4) schedule of reinforcement with ethanol (10% v/v) or sucrose (75% w/v) presented as the reinforcer. After implantation of guide cannulae aimed at the ventral tegmental area (VTA), weekly bilateral injections of muscimol (10, 30, and 100 ng) were tested. During control conditions, response patterns for both groups were characterized by high rates that began shortly after the start of the session and terminated after approximately 10 min. Muscimol (10 ng) administration in the VTA increased the number of sucrose- but had no effect on the total number of ethanol-reinforced responses. Muscimol (30 ng) shifted the response patterns of both groups from high initial rates with early termination to slow initial rates with delayed termination, suggesting the possibility of nonspecific locomotor effects. These data suggest that ethanol- and sucrose-reinforced response totals are differentially sensitive to changes in GABAergic transmission in the VTA. The similar muscimol-induced changes in response patterns with the two reinforcers supports the hypothesis that GABAA receptors in the VTA are involved similarly in the maintenance of ethanol- and sucrose-reinforced responding. However, the failure of muscimol to increase ethanol-reinforced responding suggests that GABAergic systems in other brain regions may also be involved in the changes in ethanol intake seen following peripheral administration of GABAmimetic drugs.

Alcohol Drinking↗

PubMed1996

Effect of amphetamine on behavior maintained by sucrose: interaction of reinforcement schedule and food restriction.

A multiple schedule (Mult FR 10 VI 30") was employed to examine the interaction of reinforcement schedule and food restriction on amphetamine's effects on lever pressing behavior. High response rates were observed in fixed ratio (FR) 10 components. Significantly lower response rates were observed under the variable interval (VI) 30" schedule. In the nonrestricted feeding condition, significant decreases in high rate FR 10 responding occurred after administration of 1.0 mg/kg amphetamine while lower rates under the same schedule were increased by 0.30 and 1.0 mg/kg amphetamine. In contrast, VI 30" responding was minimally effected at any amphetamine dose. Food restriction resulted in significant increases in responding in both schedule components. Under food restriction, significant decreases in responding were observed only in the FR 10 components at the highest amphetamine dose. The data indicate that amphetamine produced rate-convergent effects and the susceptibility of the animal to these effects was dependent on the schedule of reinforcement and food restriction.

Animals↗