Biomedical subjects

Herman H Samson

Publications and source records attributed to Herman H Samson.

16 recordsLinked to original sources

PubMed2003

Assessment of sucrose and ethanol reinforcement: the across-session breakpoint procedure.

We have demonstrated previously that the use of an across-session progressive ratio procedure yields breakpoint values for 10% ethanol (10E) that are stable and comparable to those measured for other drugs of abuse [Alcohol. Clin. Exp. Res. 23 (1999) 1580]. The aims of the present experiment were twofold: (1). to determine whether this procedure is sensitive to changes in reinforcer magnitude using a reinforcer previously demonstrated to affect operant responding in a predictable fashion and (2). to determine whether ethanol reinforcement produced similar changes in behavior. Male, Long-Evans rats were trained to respond for either 3% sucrose (3S) or 10E using the sipper tube appetitive/consummatory procedure where the completion of a single response requirement results in access to a liquid solution for 20 min. Three successive breakpoints were determined for this "baseline" solution by increasing the response requirement each day until it was not completed. The concentration of the solutions was then manipulated such that breakpoints for the Sucrose Group were assessed for 1%, 3%, 5% and 10% sucrose, and breakpoints for the Ethanol Group were assessed for 2%, 5%, 10% and 20% ethanol. The concentration manipulation showed that sucrose concentration had a greater impact on seeking and consumption than did ethanol concentration. Breakpoints in the Sucrose Group were highly correlated with sucrose concentration, whereas in the Ethanol Group, breakpoint was unrelated to ethanol concentration. Ethanol intake patterns suggested that pharmacological factors might have been regulating intake, and that when physiologically detectable amounts of ethanol were consumed, there was a dissociation between seeking and intake with slightly elevated ethanol seeking. Overall, the across-session breakpoint procedure confirmed that sweet taste was highly related to seeking and consumption, whereas ethanol-motivated responding may be controlled by different regulatory mechanisms that are distinct to seeking and consumption.

Animals↗

PubMed2003

Dopaminergic involvement in medial prefrontal cortex and core of the nucleus accumbens in the regulation of ethanol self-administration: a dual-site microinjection study in the rat.

The complex mesolimbic-mesocortical system involved with behavioral selection has been implicated in the control of ethanol self-administration. However, the nature of the interactions within this multiple-structured system in ethanol intake regulation remains unclear. Although the role of dopamine (DA) in the prefrontal cortex and the nucleus accumbens has been examined individually, the interaction of DA activity in both structures at the same time remains to be examined. Male, Long-Evans rats were initiated to self-administer ethanol in an operant situation using the sucrose-substitution procedure. Following initiation, bilateral cannula guides were located to allow microinjection in the medial prefrontal cortex (mPFC) and the core of the nucleus accumbens. The DA D2/D3 agonist quinpirole (10.0-microg dose in the prefrontal cortex; 4.0-microg dose in n. accumbens) and the D2 antagonist raclopride (0.05-microg dose in prefrontal cortex; 1.0-microg dose in the nucleus accumbens) were then tested in each site alone and in combination in both sites in each rat. Changes in total responding, ethanol intake, and the pattern of responding were analyzed. Single-site injections replicated most of our previous findings for these doses. Changes in single-site effects were found when dual-site injections were performed, with altered input from the prefrontal areas impacting the effects of accumbens injections. Based on these interactions, our hypothesis that the prefrontal area is involved with the onset and offset of drinking, while the nucleus accumbens is involved with maintaining the ongoing behavior, remains viable.

Alcohol Drinking↗

PubMed2003

Behavioral measures of alcohol self-administration and intake control: rodent models.

This review provides a brief historical overview of the behavioral paradigms that have been used to study alcohol consumption using rats as subjects, and then critically evaluates these models' ability to address the complexities involved in ethanol-seeking and self-administration. Many of these models have been influenced by a "behavioral pharmacology" approach, and therefore have studied oral ethanol reinforcement in a manner similar to food and water reinforcement. Because of this, these models have failed to adequately assess the complex seeking responses that are an integral part of ethanol-motivated behaviors. As an alternative, an appetitive-consummatory approach that procedurally separates and measures the two phases of behavior is suggested, and recent data using this model are reviewed. It is important that animal models that are to be used to evaluate underlying physiological mechanisms of the control of ethanol self-administration accurately address all of the complex behaviors that are involved in intake control.

Alcohol Drinking↗

PubMed2003

Ethanol and sucrose self-administration components: effects of drinking history.

Results of previous studies have shown that when rats consume higher concentrations of ethanol during initiation both the amount consumed and the pattern of consumption change with the return to a lower concentration. In this study, an across-sessions breakpoint procedure in the sipper-tube model was used to examine the effect that experience with drinking higher concentrations (a concentration manipulation) of both ethanol and sucrose had on appetitive and consummatory behaviors. A follow-up study was then conducted in the ethanol-consuming group with across-session breakpoint and intake examined before, during, and after a 3% sucrose/10% ethanol solution was presented in the sipper tube. As ethanol concentration increased, intake was not changed. Exposure to higher ethanol concentrations had no effect on the amount of 10% ethanol consumed when retested. The exposure tended to increase appetitive behavior (breakpoint), but this effect was not unique to ethanol, as rats self-administering 3% sucrose showed a similar increase. When the combined ethanol-sucrose solution was available, a significant increase in both intake and appetitive responding occurred; however, there was no change from prior intake or breakpoint when 10% ethanol was retested. That the addition of sucrose to the ethanol solution significantly increased appetitive and consummatory behaviors supports the suggestion that the composition of the alcoholic beverage can have a strong influence over the control of self-administration. Because most consumption of ethanol by human beings is in solutions that contain mixers that alter the taste of the solution, this taste factor needs to be considered in the regulation of ethanol drinking.

Alcohol Drinking↗

PubMed2003

New neuronal networks involved in ethanol reinforcement.

This article represents the proceedings of a symposium at the 2002 ISBRA/RSA meeting in San Francisco. The organizers were Kalervo Kiianmaa and Andrey E. Ryabinin. The chairs were Kalervo Kiianmaa and Jörgen A. Engel. The presentations were (1) The role of opioidergic and dopaminergic networks in ethanol-seeking behavior, by Kalervo Kiianmaa and Petri Hyytiä; (2) Interaction between the dopamine systems in the prefrontal cortex and nucleus accumbens during ethanol self-administration, by Herman H. Samson; (3) Neurochemical and behavioral studies on ethanol and nicotine interactions, by Jörgen A. Engel, Lennart Svensson, Bo Söderpalm, and Anna Larsson; (4) Involvement of the GABA receptor in alcohol reinforcement in sP rats, by Giancarlo Colombo and Giovanni Vacca; (5) Neuroactive steroids and ethanol reinforcement, by Deborah A. Finn, and (6) Potential contribution of the urocortin system to regulation of alcohol self-administration, by Andrey E. Ryabinin and Ryan K. Bachtell.(B)

Alcohol Drinking↗

PubMed2003

Effects of self-administered ethanol or water preloads on appetitive and consummatory behavior in the alcohol-preferring (P) rat.

OBJECTIVE: Ethanol intake control in the selected alcohol-preferring lines of rats appeared to have shifted in some lines for both increased ethanol seeking and increased consumption once ethanol was available. It was unknown whether a small preload of ethanol would alter either the seeking or the consumption in a selected line. This study examined this issue. METHOD: Alcohol-preferring (P) rats from Indiana University School of Medicine were initiated to drink ethanol using a sucrose-substitution procedure and a single daily limited-access trial. Following 30 responses on a lever, a sipper tube containing 10% ethanol extended into the operant chamber for 20 minutes. Self-administered ethanol and water preloads were tested prior to either a regular session or an extinction session. In extinction sessions, no access to the sipper tube occurred, and the number of responses occurring during 20 minutes was taken as a measure of ethanol seeking. RESULTS: The ethanol and water preloads had no effect on the following ethanol consumption at any time during the experiment. However, the first two ethanol preloads significantly reduced extinction responding, which did not recover to the levels observed prior to the preload tests. CONCLUSIONS: The data support the conclusion that ethanol seeking in the P rat can be influenced by environmental history, whereas consummatory behavior appears to be under more explicit genetic control. This gene-environment interaction suggests that, in the P rat, seeking behavior, initially set at higher levels than observed for nonselected lines, can be modified by certain environmental experiences.

Animals↗

PubMed2002

Reinstatement of ethanol seeking responding after ethanol self-administration.

Understanding the processes related to resumption of alcohol-seeking behavior after a small, single exposure to alcohol could be important in treating alcoholic relapse. We used a new ethanol self-administration model to determine the potential role of ethanol self-administration in reinstatement of seeking behavior. Long-Evans rats were initiated to self-administer either 10% ethanol or 3% sucrose in a sipper procedure. This procedure required that the rat make a fixed number of lever presses to gain access to a sipper tube for 20 min. Patterns of responding and tube-licking as well as volume intakes were recorded. Both within-session and across-session extinction/reinstatement procedures were tested with a brief ethanol self-administration exposure as the reinstatement event. Self-administration of small amounts of 10% ethanol (1.3 ml) in ethanol-trained rats and small amounts of 3% sucrose (1.4 ml) in sucrose-trained rats resulted in modest reinstatement lever pressing. Although some reinstatement occurred, the amounts of lever pressing were minimal. These findings support the suggestion that self-administered ethanol in this experimental paradigm does not increase ethanol-seeking behavior.

Administration, Oral↗

PubMed2002

Ethanol consumption in the female Long-Evans rat: a modulatory role of estradiol.

The examination of various gonadal hormone manipulations on ethanol intake in human subjects and in rodent models has resulted in disparate findings. In the present study, we examined the effects of ovariectomy and subsequent estradiol (E(2)) replacement on ethanol intake in a within-subject design, as well as assessed the relevance of reproductive status on the efficacy of an E(2) stimulus in eliciting consumption. Female Long-Evans rats (n = 24) were given access to 10% ethanol and water in a continuous-access paradigm. After establishment of baseline intake values, rats were divided into four groups: sham/placebo (Shm+P), sham/estradiol (Shm+E(2)), ovariectomized/placebo (Ovx+P), and ovariectomized/estradiol (Ovx+E(2)). Rats in the Ovx+P group were found to have a large and permanent decline in ethanol intake that persisted more than 3 months postsurgery. Administration of E(2) to Ovx+E(2) rats was associated with restoration of ethanol consumption to baseline levels. When Shm+E(2) and Ovx+E(2) groups were compared, reproductive status was found to be a determining factor in the efficacy of E(2) to elicit ethanol intake. Together, these findings provide evidence that ovarian hormones, particularly estradiol, exert activational effects on estrogen-responsive substrates to modulate ethanol consumption in the adult female rat.

Alcohol Drinking↗

PubMed2002

Ethanol self-administration in Maudsley reactive and Maudsley nonreactive inbred rats.

This study was performed to investigate ethanol self-administration in inbred Maudsley rats, which were selected for differences in stress susceptibility and which often differ in their home cage ethanol consumption. Adult, male, Maudsley reactive (MR/Har) and Maudsley nonreactive (MNRA/Har) rats were tested in a standard protocol for the sucrose-substitution procedure for the initiation of self-administration of ethanol in an operant setting. Before and after initiation for self-administration in the operant setting, rats were tested for home cage consumption of 10% (vol./vol.) ethanol in a two-bottle test for 14 consecutive days. During the sucrose-substitution procedure, MNRA/Har rats consumed more sucrose and ethanol than did MR/Har rats. In addition, MNRA/Har rats self-administered a greater amount of ethanol during a concentration manipulation with the use of a fixed ratio (FR) 4 response requirement. However, both strains self-administered low amounts of 10% ethanol (MNRA/Har, 0.15 g/kg/day; MR/Har, 0.08 g/kg/day) after concentration manipulation compared with those observed in outbred rats and alcohol-preferring rats tested under identical conditions in other studies. Both MR/Har and MNRA/Har rats markedly increased their ethanol intake in the home cage after the initiation protocol, but there was no difference between MR/Har and MNRA/Har on that measure. The failure of MR/Har rats to self-administer ethanol was inconsistent with their home cage drinking in other studies, and this is distinctly different from the self-administration pattern of high-alcohol-drinking rat lines tested in this paradigm.

Alcohol Drinking↗

PubMed2002

Separate measures of ethanol seeking and drinking in the rat: effects of remoxipride.

Remoxipride, a dopamine D(2) antagonist, decreases responding that results in the presentation of small amounts (approximately 0.1 ml) of ethanol in limited-access paradigms. This type of operant response is a combined appetitive/consummatory response that is differentially affected by changing stimulus properties of consumed ethanol (i.e., taste, pharmacology) over the course of the session. In the present experimental design, ethanol-directed appetitive and consummatory responses were procedurally separated to investigate the specific effects of remoxipride on these distinct behaviors. Male Long-Evans rats were trained to make a series of lever-press responses once each day that resulted in access to a sipper tube spout containing 10% ethanol for 20 min. Three doses of remoxipride were tested: 5.0, 10.0, and 15.0 mg/kg (-30 min, i.p.). In Experiment 1, a response requirement of 20 was used, and both reinforced and nonreinforced sessions were examined. In nonreinforced sessions, subjects were permitted to lever press for 20 min, after which the session ended without sipper tube presentation. These sessions were conducted to remove the possibility that limiting responding might obscure a drug effect on the seeking response. In Experiment 2, a low response requirement (4) was used to investigate the effects of remoxipride on ethanol intake. Average baseline ethanol intake (Experiment 1) was 0.69 g/kg, with blood ethanol concentrations at the end of the session at 64 mg%. At all doses tested, remoxipride had no effect on the measures of ethanol consumption (e.g., total intake, lick latency, lick rate) in either experiment. However, remoxipride dose dependently decreased the number of appetitive responses made, while having no effect on response latency or rate, during both reinforced and nonreinforced sessions in Experiment 1. In these experiments, the systemic antagonism of the dopamine D(2) receptor decreased ethanol seeking without causing a general impairment of motor function. The procedural separation of seeking and intake responses revealed that appetitive responding was more sensitive than consummatory responding to remoxipride treatment.

Alcohol Drinking↗

PubMed2002

Repeated nicotine injections decrease operant ethanol self-administration.

Nicotine and alcohol are two of the most used drugs in the United States. However, it is not clear whether the co-use of these drugs is due to pharmacological or environmental reasons, or perhaps related to both. Although results from previous studies in animal models seem to indicate that nicotine has an effect on ethanol consumption, little has been done to determine how nicotine affects appetitive and consummatory phases of ethanol self-administration. In this study, we examined the effect of repeated treatment with nicotine (0, 0.35, and 0.7 mg/kg, s.c.), given 30 min before a daily operant session, on appetitive and consummatory phases of Long-Evans rats self-administering 10% (vol./vol.) ethanol in a sipper-tube model. Ethanol intake (consummatory phase) decreased at both doses of nicotine tested, and lever pressing (appetitive phase) decreased after injection of the high dose of nicotine. These results support the suggestion that nicotine affects ethanol self-administration. However, in this model, the findings demonstrate a reduction in drinking, rather than the enhancement that has been shown in findings obtained from other studies.

Animals↗

PubMed2002

Ethanol- and sucrose-reinforced appetitive and consummatory responding in HAD1, HAD2, and P rats.

INTRODUCTION: Ethanol-preferring (P) rats and high-alcohol-drinking (HAD1 and HAD2) rats have been selectively bred to consume greater amounts of ethanol than nonselected rat strains. These three rat lines also show increased levels of responding for ethanol in operant paradigms that assess a combined appetitive/consummatory response. METHODS: The present experiment used a model of reinforced responding that procedurally separates the appetitive, or seeking, response requirement from consummatory responding to compare seeking and intake responding in P and HAD rats. Subjects (n = 7 or 8 per group) were trained to make 25 lever-press responses, which were followed by 20 min of access to a sipper tube spout containing either 10% ethanol (10E) or (in separate groups of subjects) 3% sucrose (3S). After training, a single nonreinforced session was conducted to assess the limit to appetitive responding under extinction conditions. After this single nonreinforced session, three successive across-session breakpoint determinations were made for 10E and 3S by increasing the response requirement over days until subjects failed to complete the requirement. A final extinction session was then conducted. RESULTS: Appetitive responding during both the nonreinforced and breakpoint sessions indicated that P rats made significantly more responses overall than HAD rats in both the ethanol and sucrose groups. P rats also consumed more sucrose than HAD rats, with no differences in ethanol consumption between the lines (1.0-1.5 g/kg/20 min). Appetitive responding in the HAD rats in the ethanol groups was comparable to that reported previously for nonselected Long-Evans rats. CONCLUSIONS: These findings indicate that appetitive and consummatory processes are distinct and that P rats have an increased tendency to both seek and drink ethanol and sucrose solutions, making this selected line useful when modeling both "craving" and "loss of control" related behaviors involved in excessive alcohol consumption.

Alcohol Drinking↗

PubMed2002

Operant self-administration of ethanol in Sardinian alcohol-preferring rats.

BACKGROUND: "Work" for ethanol, that is, the ability of a laboratory animal to press a lever to gain access to ethanol, has been proposed as (a) a requirement for definition of an animal model of alcoholism and (b) a measure of ethanol-reinforcing properties. The present study evaluated oral self-administration of ethanol under an operant (lever pressing) procedure in selectively bred Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats. METHODS: Rats from both lines were initiated to self-administer 10% ethanol, on a fixed ratio 1 schedule and in daily 30 min sessions, by using the Samson sucrose fading procedure. Subsequently, rats were exposed to increasing concentrations of ethanol up to 30% on a fixed ratio 4 schedule. Finally, the extinction responding for ethanol, defined as the maximal number of lever responses reached by each rat in the absence of ethanol reinforcement, was determined. RESULTS: The results indicated that sP rats acquired and maintained lever pressing for ethanol, self-administering mean amounts of ethanol in the range of 0.6 to 1.1 g/kg/session, which gave rise to mean blood ethanol levels in the 30 to 45 mg% range. Extinction responding for ethanol in sP rats averaged 73. In contrast, once sucrose was faded out, sNP rats displayed minimal levels of responding for ethanol, and extinction responding averaged 6. CONCLUSIONS: The results of the present study extend to the sP/sNP rat lines the finding that ethanol can be established as a reinforcer in selectively bred alcohol-preferring rats, whereas it has modest, if any, reinforcing properties in alcohol-nonpreferring rats.

Alcohol Drinking↗

PubMed2002

Effects of self-administered alcohol or sucrose preloads on subsequent consumption in the rat.

OBJECTIVE: The initial drink of alcohol is often conceptualized as "priming" the individual for the following drinking bout. For the alcoholic, this priming effect has been considered a key for the loss of control that then occurs. Although there have been a few animal studies examining the effects of an investigator-administered ethanol preload on subsequent ethanol self-administration, the effects of a small self-administered oral preload on subsequent consumption have not been examined. METHOD: Adult, male rats, initiated to self-administer ethanol using the sucrose-substitution procedure, were given brief access periods to drink ethanol or water, 5 minutes prior to a second opportunity to press a lever for an additional 20-minute access to a 10% ethanol solution. A second group of rats were trained to press a lever to gain access to a 3% sucrose solution, and the effects of sucrose or water preloads were examined and compared with results in the ethanol group. RESULTS: In the ethanol group, both the ethanol and water preload intakes increased as preload access time increased and were not different from each other. However, ethanol preloads at the longer access times (60 seconds and 120 seconds) decreased subsequent ethanol consumption and at the highest time also affected ethanol-seeking behavior. Equal volumes of water intake at these longer access times had no effects on subsequent ethanol consumption. In the sucrose group, sucrose preload intakes increased as access time increased, but water preload intakes did not. Neither sucrose nor water preloads had any effect on subsequent sucrose consumption. CONCLUSIONS: The data failed to find any priming effect of ethanol preloads in terms of increased subsequent ethanol consumption. It appears that a major factor in the regulation of ethanol intake for the rat in this training procedure is the postingestional effects of ethanol, because taste stimuli did not appear to be important. However, it appears that these ethanol postingestive stimuli are not identical to those involved in the regulation of sucrose consumption.

Alcohol Drinking↗

PubMed2002

Microanalysis of ethanol self-administration: estrous cycle phase-related changes in consumption patterns.

BACKGROUND: Female rodent and reproductive cycle-related patterns in ethanol consumption have been identified grossly, but the regulatory processes that underlie these patterns remain to be clarified. The evaluation of consummatory bout dynamics may be useful in determining the effects of a changing endogenous state (ovarian hormone fluctuations) on ethanol consumption patterns. This study assessed the microstructural components of ethanol intake patterns across the estrus cycle. METHODS: Cumulative licking of 13 female Long-Evans rats was recorded during continuous access (22 hr/day) to 10% ethanol and tap water solutions throughout a 10 week period. Drinking bouts were defined as 20 or more successive licks separated by less than a 60 sec pause. Vaginal smears were obtained daily from each rat between 1100 and 1130 hr to assess estrus cycle phase. ANOVAs were conducted to evaluate estrus cycle effects on consumption pattern parameters. RESULTS: Total daily ethanol intakes were unaffected by estrus cycle phase. Ethanol bout frequency was significantly greater during proestrus compared with all other phases, whereas ethanol bout sizes were significantly attenuated during proestrus compared with estrus and diestrus. Experience with ethanol was associated with a significant decline in bout frequency and a significant elevation in bout size across all cycle phases, which indicated that initiation of ethanol self-administration occurred over time. A significant main effect of hour and a cycle phase by hour interaction were found for the temporal distribution of ethanol lick responses throughout the estrus cycle, and a progressive shift in lick patterns evolved between estrus and the subsequent proestrus. CONCLUSIONS: The estrus cycle phase-related changes in the microstructural components of ethanol intake suggest that female rats experience periods of altered sensitivity to the neurobiological and reinforcing effects of ethanol. Furthermore, these findings implicate cyclical fluctuations in ovarian hormones and other neuromodulators in the regulation of ethanol consumption patterns throughout the estrus cycle of the female rat.

Alcohol Drinking↗

PubMed2002

Effect of ethanol self-administration on mu- and delta-opioid receptor-mediated G-protein activity.

BACKGROUND: This study examined the effects of ethanol self-administration on mu- and delta-opioid receptor-mediated G-protein activity in specific brain regions of male Long Evans rats. METHODS: Rats were trained to self-administer ethanol by using a home-cage modification of the sucrose substitution paradigm. After 30 to 40 days of sucrose or sucrose/15% ethanol self-administration (20 min sessions, Monday-Friday), rats were killed for autoradiographic assays. Coronal sections of brains from sucrose and ethanol self-administering rats were collected and processed for basal and mu- and delta-stimulated [35S]guanosine-5'-O-(gamma-thio)-triphosphate (GTPgammaS) binding. Sections were exposed to film and then analyzed by using computer-assisted densitometry to determine levels of basal and agonist-stimulated [35S]GTPgammaS binding. RESULTS: Mu-opioid-stimulated [35S]GTPgammaS binding was decreased in the prefrontal cortex of brains from ethanol compared with sucrose self-administering rats. Mu-opioid-stimulated [35S]GTPgammaS binding was unchanged in the cingulate cortex, caudate-putamen, nucleus accumbens, amygdala, hypothalamus, thalamus, and locus ceruleus of ethanol compared with sucrose self-administering rats. Basal and delta-opioid-stimulated [35S]GTPgammaS binding did not differ between the two groups in the prefrontal cortex or any other region analyzed. CONCLUSIONS: These data demonstrate decreased mu-opioid-mediated G-protein activity in the prefrontal cortex of ethanol self-administering rats and suggest an interaction between ethanol and mu-opioid receptors in this region.

Animals↗