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PubMed1999

Examination of factors mediating the transition to behaviorally correlated nucleus accumbens cell firing during cocaine self-administration sessions in rats.

We have previously reported that at the initiation of cocaine self-administration sessions, neurons in the nucleus accumbens (NA) exhibit a spontaneous transition in firing rate from activity unrelated to the reinforced response, to one of four types of patterned discharges (Carelli RM, King VC, Hampson RE, Deadwyler SA. Firing patterns of nucleus accumbens neurons during cocaine self-administration in rats. Brain Res 1993;626:14-22; Carelli RM, Deadwyler SA. Dose-dependent transitions in nucleus accumbens cell firing and behavioral responding during cocaine self-administration sessions in rats. J Pharm Exp Ther 1996;277(1):385 393; Carelli RM, Deadwyler SA. Cellular mechanisms underlying reinforcement-related processing in the nucleus accumbens: electrophysiological studies in behaving animals. Pharmacol Biochem Behav 1997;57:(2)1-10). This transition in NA cell firing is cocaine dose-dependent and is accompanied by a shift from high response rates at the start of the session ('Load-up' behavior) to a lower steady rate of responding thereafter (termed 'Session' phase responding). Two experiments were conducted to examine further factors that may mediate this process. Experiment 1 examined the effects of pre-session, response-independent delivery of cocaine on behavioral/neural transitions. Results revealed an absence of Load-up responding and the immediate onset of NA patterned activity at the start of the session. Experiment 2 examined the involvement of dopamine D1 versus D2 receptors in mediating the corresponding behavioral/neural transitions. Animals were pretreated with either saline, the dopamine D1 receptor antagonist SCH23390 (2.5-20 microg/kg, s.c.), or the dopamine D2 receptor antagonist eticlopride (2.5-20 microg/kg, s.c.) 30 min prior to the cocaine (0.33 mg/inf) self-administration session. SCH23390 significantly increased the number of Load-up responses at 10 and 20 microg/kg and the number of responses following the Load-up phase (i.e. during the Session phase) at 5, 10, and 20 microg/kg. Eticlopride increased the number of Session responses (5, 10, and 20 microg/kg), but did not alter the number of Load-up responses at any dose tested. The transition in NA cell firing corresponded with the shift in behavioral responding and was delayed within the session following SCH23390 but not eticlopride pretreatment. These findings support the notion that cocaine self-administration sessions in rats consists of two distinct behavioral phases that are mediated by different neurophysiological mechanisms operating in the NA.

Analysis of Variance↗

PubMed1997

The effects of d-amphetamine on the reinforcing effects of food and fluid using a novel procedure combining self-administration and location preference.

Using a laboratory animal procedure designed to measure two aspects of behavior related to commodity seeking (self-administration and location preference), five individually housed adult rhesus monkeys lived in three chambers: fluid- (sweetened Kool-Aid solution) related cues and oral fluid self-administration were specific to one end chamber, food pellet-related cues and food self-administration were specific to the other end chamber, and no food cues or fluid cues were available in the middle chamber. Throughout the 10 h experimental day, monkeys experienced multiple food, fluid, choice (food versus fluid), and no-commodity sessions. Oral d-amphetamine (AMPH; 0.5-1.5 mg/kg) or placebo was administered before the sessions to determine if this anorectic drug would differentially alter food and fluid self-administration. The effects of AMPH on the length of time monkeys spent in each chamber, when the stimulus lights indicating commodity availability were not illuminated (location preference) were also determined. AMPH decreased both food and fluid self-administration, but responding for fluid was reduced to a greater extent than responding for food. AMPH, however, increased the length of time monkeys spent in the food chamber, even when no stimulus lights indicating food availability were illuminated. The increase in the length of time spent in the food chamber was predicted by the decrease in the number of fluid deliveries, not the number of food deliveries. These results indicate that the relationship between self-administration and location preference, as measures of reinforcing effects, is not completely concordant. The current procedure may prove useful in comparing these two measures of reinforcing effects with other reinforcers.

Animals↗

PubMed1984

Effects of pentobarbital and d-amphetamine on oral phencyclidine self-administration in rhesus monkeys.

Three rhesus monkeys self-administered phencyclidine (0.25 mg/ml) during daily 3-hr sessions. Water was also available under a concurrent fixed-ratio (FR) 16 schedule. In Experiment 1, saline or three doses of pentobarbital (2.5, 5 or 10 mg/kg) were injected 10 min before phencyclidine (and water) self-administration sessions. The 2.5 mg/kg pentobarbital dose increased phencyclidine-maintained responding, the 5 mg/kg dose produced mixed effects among the three monkeys, and the 10 mg/kg dose consistently decreased phencyclidine-maintained responding. Subsequently, a saccharin solution (0.03% wt/vol) replaced phencyclidine, and the pentobarbital pretreatment procedure was repeated. Pentobarbital produced dose-related decreases in saccharin-maintained responding. In Experiment 2, saline or three doses of d-amphetamine (0.05, 0.1 or 0.2 mg/kg) were injected 10 min before the phencyclidine self-administration sessions. The 0.05 mg/kg dose produced increases in phencyclidine-maintained responding, while the two higher doses produced dose dependent decreases in responding. When a saccharin solution (0.03%, wt/vol) replaced phencyclidine during the daily sessions, d-amphetamine produced only dose-related decreases in saccharin-maintained responding. These results indicate that pentobarbital and d-amphetamine have a biphasic effect on phencyclidine-maintained behavior; low doses increased responding and high doses decreased responding.

Animals↗

PubMed1996

Neuronal spike activity in rat nucleus accumbens during cocaine self-administration under different fixed-ratio schedules.

Chronic ensemble recording techniques were used to investigate neuronal activity in the nucleus accumbens in freely moving rats during different cocaine self-administration schedules. The issue of concern in this study was the role of nucleus accumbens in initiating and sustaining cocaine self-administration. Specifically, to determine the nature of the neuronal activity, either motor or motivational, which precedes the multiple bar presses required to self-administer cocaine and of the post-lever press neuronal response, we used conventional fixed ratio-5, fixed ratio-10, and modified fixed ratio-3 schedules. In the modified fixed ratio-3 schedule, the first lever press resulted in retraction of the lever for 2 s; the second lever press retracted the lever and turned on a cue light; the third lever press turned off the cue light and delivered cocaine (1.0 mg/kg) intravenously. In the fixed ratio-5 and -10 schedules, rats continuously pressed the lever 5 or 10 times, respectively, to obtain a single infusion of cocaine. Phasic alterations in neural spike activity were observed in 50% of nucleus accumbens neurons before (termed "anticipatory" responses) and after lever pressing for cocaine self-administration. Neurons with anticipatory responses typically exhibited such responses for all lever presses in the modified fixed ratio-3, fixed ratio-5, and fixed ratio-10 schedules, but instances were found when the activity correlate was absent. In addition, some neurons had a prominent alteration in firing rate lasting 1-5 min after cocaine self-administration, and some of these neurons also had anticipatory responses. When cocaine was eliminated during self-administration sessions, the post-lever press inhibitory responses were largely abolished or even reversed, whereas anticipatory responses were not markedly changed when rapid lever presses occurred before behavior ceased. Post-cocaine inhibitory responses compared between self-administered and passively administered cocaine were not significantly different between these two conditions. The results suggest that nucleus accumbens may be involved in initiating general reward-seeking behaviors and action which are not exclusively associated with cocaine self-administration. Moreover, the neuronal responses in the nucleus accumbens to cocaine self-administration may play an essential role in maintaining cocaine reinforcement.

Animals↗

PubMed2000

Dextromethorphan alters methamphetamine self-administration in the rat.

Various lines of evidence indicate that methamphetamine (METH) self-administration in rats is under dopaminergic control, and NMDA receptors have been shown to control the release of dopamine at its synapse. Consequently, the aim of this study was to observe the effects of dextromethorphan (DM), a non-competitive NMDA antagonist, in rats self-administering METH. The hypothesis was that acute pretreatment of DM (25 mg/kg) would alter response to METH. DM significantly altered self-administration by reducing the number of correct responses for three METH self-administration doses (0.05, 0.1, 0.25 mg/kg). The same pretreatment did not affect responding for food reward. These findings show that the DM was able to selectively alter METH self-administration.

Animals↗

PubMed2001

Social defeat alters the acquisition of cocaine self-administration in rats: role of individual differences in cocaine-taking behavior.

RATIONALE: It is known that social defeat can modulate cocaine self-administration. However, it is unclear whether this psychosocial stressor affects drug-taking behavior to the same extent across all individual animals, particularly those with differing propensities to self-administer psychostimulants. OBJECTIVE: This study examined the effect of social defeat on cocaine self-administration in animals that differ in novelty-seeking behavior that predicts differences in drug self-administration. METHODS: Male Sprague-Dawley rats were first classified into high-responder (HR) and low-responder (LR) groups. HR and LR rats were categorized based on their locomotor activity in a novel environment, with HR rats exhibiting higher locomotor activity than LR rats. Then, male rats were exposed on four occasions to an aggressive Long Evans male rat over the course of 4 days. Control rats were not exposed to the social defeat. All rats were subsequently implanted with jugular catheters and 3 days later placed into the self-administration box to study the acquisition of cocaine self-administration (0.25 mg per infusion). RESULTS: HR non-defeated animals self-administered more cocaine than the LR non-defeated animals. Following social defeat, the acquisition of cocaine self-administration is significantly delayed in HR rats and enhanced in LR rats. CONCLUSION The unique patterns of responsiveness in the HR and LR animals suggest that social defeat plays a role of equalizer of individual differences in drug-taking behavior.

Animals↗

PubMed2001

Effects of naltrexone and Ro 15-4513 on a multiple schedule of ethanol and Tang self-administration.

BACKGROUND: Both the opioid antagonist, naltrexone, and GABAA/benzodiazepine-site negative modulator, Ro 15-4513, decrease ethanol self-administration in rodents and nonhuman primates. However, the selectivity of these drugs for decreasing ethanol self-administration relative to reducing responding maintained by other reinforcers in primates is not clear. The present study used a multiple schedule self-administration procedure in cynomolgus monkeys to examine the selectivity of naltrexone and Ro 15-4513 for reducing ethanol self-administration relative to an orange flavored sugar-free sweetened solution (Sugar-free Tang). METHODS: Six adult cynomolgus monkeys were trained to self-administer 4% (w/v) ethanol and 4% or 6% (w/v) Tang under a multiple schedule of liquid access. The effect of acute administration of naltrexone (0.1, 0.3, 1, 3 mg/kg) was examined. The effect of 15 days of chronic, 1 mg/kg naltrexone on ethanol and Tang self-administration was then examined in four monkeys. Acute administration of Ro 15-4513 (0.01, 0.03, 0.1, 0.3 mg/kg) as well as 15 days of chronic administration of 0.1 mg/kg Ro 15-4513 was also examined in four monkeys. RESULTS: Ethanol and Tang were self-administered at similar volumes and patterns under baseline conditions. Acute naltrexone administration significantly decreased total session ethanol and Tang intake as well as the number and volume of ethanol and Tang drinks. Chronic naltrexone also significantly decreased ethanol and Tang intake. Ethanol, but not Tang, drink volume was significantly decreased by chronic 1 mg/kg naltrexone pretreatment. The number of ethanol and Tang drinks and drink duration were not significantly decreased by chronic naltrexone. Acute Ro 15-4513 pretreatment significantly decreased ethanol and Tang intake, mean drinks and median drink duration. Chronic 0.1 mg/kg Ro 15-4513 pretreatment significantly decreased total ethanol intake only during the first week of pretreatment, but it significantly decreased Tang intake for all 3 pretreatment weeks. CONCLUSIONS: Similar to rodent studies, acute and chronic naltrexone and Ro 15-4513 reduced ethanol and Tang intake in cynomolgus monkeys. However, unlike rodent studies, neither drug showed selectivity for reducing ethanol intake compared with a comparison reinforcer. These differences highlight the need for testing putative ethanol abuse treatment drugs under diverse conditions and multiple species before undertaking human clinical trials.

Animals↗

PubMed2001

Neuropeptide-Y in the paraventricular nucleus increases ethanol self-administration.

The paraventricular nucleus (PVN) of the hypothalamus is known to modulate feeding, obesity, and ethanol intake. Neuropeptide-Y (NPY), which is released endogenously by neurons projecting from the arcuate nucleus to the PVN, is one of the most potent stimulants of feeding behavior known. The role of NPY in the PVN on ethanol self-administration is unknown. To address this issue, rats were trained to self-administer ethanol via a sucrose fading procedure and injector guide cannulae aimed at the PVN were surgically implanted. Microinjections of NPY and NPY antagonists in the PVN were conducted prior to ethanol self-administration sessions. All doses of NPY significantly increased ethanol self-administration and preference, and decreased water intake. The NPY antagonist D-NPY partially reduced ethanol self-administration and completely blocked the effects of an intermediate dose of NPY (10 fmol) on ethanol intake, preference, and water intake. The competitive non-peptide Y1 receptor antagonist BIBP 3226 did not significantly alter ethanol self-administration or water intake when administered alone in the PVN but it completely blocked the effect of NPY (10 fmol) on ethanol intake. NPY infused in the PVN had no effect on ethanol self-administration when tested in rats that did not have a long history of ethanol self-administration. The doses of NPY tested produced no effect on food intake or body weight measured during the 24-h period after infusion in either ethanol-experienced or ethanol-inexperienced rats. These results indicate that elevation of NPY levels in the PVN potently increases ethanol self-administration and that this effect is mediated through NPY Y1 receptors.

Alcohol Drinking↗

PubMed1998

Self-administration of drugs for cystic fibrosis.

Self-administration of medication encourages individuals to participate in their own health care and provides structure for regular assessment and teaching about their drugs. Patient-friendly drug leaflets can provide consistent information to patients cared for by a number of staff. Self-administration studies found in the nursing literature must be interpreted cautiously because of the lack of true experimental trials.

Adult↗

PubMed1997

Self-administration in rats allowed unlimited access to nicotine.

The purpose of the present study was to develop an animal model of nicotine self-administration that more closely approximates the conditions of human nicotine use than do existing models. In most nicotine self-administration models, rats acquire self-administration during brief daily sessions in which rapid injections of a relatively high dose of the drug, 0.03 mg/kg, serve as the reinforcer. The present study examined nicotine self-administration in rats that acquired the behavior while having virtually unlimited access to injections of a relatively low dose of the drug; the rats did not have any prior operant training or shaping. Under these conditions, rats readily acquire nicotine self-administration at doses at least as low as 0.00375 mg/kg per injection, and they self-administer throughout the active portion of their light cycle. The daily nicotine intake of rats, which ranged from 0.18 to 1.38 mg/kg per day, appears to be comparable to that of human smokers.

Animals↗

PubMed1995

Short-term cocaine self administration alters striatal gene expression.

Rats self-administered cocaine or received saline during 3 daily 5 h sessions and were euthanized 1 h after the final session. Quantitative in situ hybridization revealed that cocaine self-administration increased levels of preprodynorphin, but not preproenkephalin, c-fos, or zif/268 mRNAs in a patchy pattern in the dorsal striatum. These data demonstrate that the regulation of preprodynorphin gene expression is dissociable from that of c-fos and zif/268 in dorsal striatum following short-term cocaine self-administration.

Animals↗

PubMed2000

Heroin self-administration under a second-order schedule of reinforcement: acquisition and maintenance of heroin-seeking behaviour in rats.

RATIONALE: Second-order schedules of heroin self-administration provide a method of measuring heroin-seeking behaviour independently of the effects of the drug on motor behaviour and of investigating the role of heroin-associated stimuli in such heroin-seeking behaviour. OBJECTIVES: These experiments aimed to establish a second-order schedule of heroin self-administration in rats, similar to that already established in this laboratory for cocaine self-administration and to investigate the role of discrete heroin-associated stimuli in the maintenance of heroin-seeking behaviour under a second-order schedule of reinforcement. METHODS: Heroin i.v. self-administration (0.04 mg/infusion) was initially contingent upon a lever press, and each infusion was paired with presentation of a 20-s light-conditioned stimulus (CS). Following acquisition of heroin self-administration, the response requirement was progressively increased so that, ultimately, responding was maintained under a fixed interval (FI) 15 min [fixed ratio (FR)5:S] second-order schedule. The effects of varying the dose of heroin (0.01 mg and 0.08 mg/infusion) and pre-treatment with the mu-opiate receptor antagonist, naloxone, on responding under a FI15(FR5:S) schedule were investigated. In addition, the role of the heroin-associated CS on responding was assessed by measuring the effects of omitting the CS during heroin-seeking behaviour and during extinction of responding, as well as the effect of CS presentation on the reinstatement of heroin-seeking behaviour following extinction. RESULTS: A second-order schedule of heroin self-administration was established. There were no clear effects on heroin-seeking behaviour of increasing or decreasing the dose of heroin. Although no effect of naloxone pre-treatment was seen on heroin-seeking behaviour during the first, drug-free interval of responding, an extinction-like pattern of responding was seen in that interval during subsequent sessions. Omission of the light CS resulted in a reduction in levels of responding for i.v. heroin, indicating its role in maintaining heroin-seeking behaviour. However, under extinction conditions, response-contingent CS presentations did not affect the rate of extinction, nor did non-contingent presentations of the CS following extinction reinstate heroin-seeking behaviour. CONCLUSIONS: These experiments have established a method of measuring heroin-seeking behaviour in rats by adopting a second-order schedule of i.v. heroin self-administration. The results indicate a relatively weak impact of discrete, heroin-associated cues on heroin-seeking behaviour relative to cocaine-seeking behaviour studied under similar conditions.

Animals↗

PubMed1996

The relationships among saccharin consumption, oral ethanol, and i.v. cocaine self-administration.

The purpose of the present experiment was to replicate previously reported observations of a relationship between saccharin consumption and oral ethanol self-administration in rats using operant measures (2,8) and to determine whether saccharin intake was related to the rate of acquisition of IV cocaine self-administration. Groups of Wistar rats selected for high and low saccharin (0.1% wt/vol) intake were tested for rate of acquisition of IV cocaine (0.2 mg/kg/infusion) self-administration using an autoshaping procedure. They were subsequently tested for self-administration of oral ethanol (8% wt/vol) under ascending fixed-ratio (FR) schedules (FR 1, 2, 4, and 8). Finally, ethanol deliveries were compared under food-deprivation and food-satiation conditions under an FR 8 schedule. Saccharin intake was redetermined after each phase of the experiment. No significant differences between high and low saccharin groups were found in rate of acquisition of IV cocaine self-administration, and there was not a significant correlation between saccharin and cocaine consumption. However, the high saccharin group drank significantly more ethanol than the low saccharin group during the FR 8 food satiation component. A significant correlation between saccharin and ethanol consumption was also found. For high and low saccharin groups, responding for ethanol increased proportionally with increases in FR such that consumption of ethanol remained relatively constant as FR increased. Ethanol consumption was significantly increased under food deprivation relative to food satiation conditions for both saccharin groups. A significant correlation between ethanol consumption and cocaine consumption was also found. Significant increases in saccharin consumption across successive saccharin consumption tests were found for both groups, although relative intake for the high and low saccharin groups remained stable throughout the experiment. These results indicate that higher ethanol intake is predicted by higher saccharin intake, but saccharin intake did not predict the rate of acquisition of IV cocaine self-administration.

Alcohol Drinking↗

PubMed2005

Cocaine and heroin ('speedball') self-administration: the involvement of nucleus accumbens dopamine and mu-opiate, but not delta-opiate receptors.

RATIONALE: The combined administration of heroin and cocaine ('speedball') is common among intravenous drug users. Dopamine receptors in the nucleus accumbens play a key role in cocaine self-administration; however, their role in speedball self-administration is unknown, as is the role of opiate receptors in this region. OBJECTIVES: The effect of blocking dopamine D1, D2, mu-opiate or delta-opiate receptors in the nucleus accumbens on the intravenous self-administration of combined heroin and cocaine was examined in rats. METHODS: Rats with bilateral cannulae implanted into the nucleus accumbens were trained to self-administer intravenous speedball (ratio of cocaine/heroin, 17:1) under a progressive ratio (PR) schedule. Prior to their self-administration session, rats were then microinjected with the dopamine D1 receptor antagonist SCH 23390 (1 and 6 nmol side(-1)), the D2 receptor antagonist raclopride (3 and 10 nmol side(-1)), the mu-opiate receptor antagonist CTOP (0.1, 0.3 and 1.0 nmol side(-1)), the delta-opiate receptor antagonist naltrindole (1.0, 3.0 and 10 nmol side(-1)) or a cocktail of SCH 23390 (1 nmol side(-1)) and CTOP (0.1 nmol side(-1)) into the nucleus accumbens. RESULTS: Microinjection of SCH 23390, raclopride or CTOP into the nucleus accumbens produced dose-dependent decreases in breakpoints under the PR schedule, while naltrindole was without effect. The highest dose of SCH 23390 also significantly reduced locomotor activity measured during speedball self-administration. The combination of SCH 23390 and CTOP significantly reduced breakpoints, while not affecting locomotor activity. CONCLUSIONS: These results indicate that dopamine and mu-opiate receptors, but not delta-opiate receptors, in the nucleus accumbens are involved in the reinforcing effects of speedball. Combined administration of D1 and mu-opiate receptor antagonists may be more selective at reducing the reinforcing effects of speedball self-administration than either drug alone.

Animals↗

PubMed1993

Blockade of the acquisition of cocaine self-administration by the NMDA antagonist MK-801 (dizocilpine).

In an attempt to assess the contribution of the NMDA receptor system to the development of cocaine self-administration, acquisition of intravenous self-administration (0.25mg/kg/infusion) was assessed in rats that received pretreatment with MK-801 (0.0, 0.1 or 0.25mg/kg). For control rats, reliable self-administration was obtained in 3-8 days of testing. These rats rapidly discriminated between depression of a lever that resulted in the delivery of cocaine and an inactive lever. Within the initial 10 day test period, most of the rats pretreated with MK-801 failed to acquire a preference for an active lever which, when depressed, resulted in a cocaine infusion: responding was generally high on both the cocaine reinforced and inactive lever. For six rats, MK-801 treatment was discontinued after 10 days. Although some of these rats had received substantial exposure to cocaine during the initial 10 days, self-administration subsequent to the termination of treatment progressed either with a time course comparable to cocaine-naive rats, or not at all. For rats that continued to receive MK-801 treatment, most failed to acquire reliable self-administration within the 18 day test period. These data suggest that the glutamatergic NMDA receptor system plays an important role in the establishment of cocaine as an effective reinforcer.

Journal Article↗

PubMed2001

High rates of midazolam self-administration in squirrel monkeys.

Although benzodiazepines are frequently abused by humans, they usually maintain lower rates of self-administration behavior in laboratory animals than other drugs of abuse such as psychomotor stimulants or barbiturates. In the present study, intravenous (i.v.) self-administration of the short-acting benzodiazepine midazolam was evaluated in squirrel monkeys. Monkeys (n = 3) initially self-administered the short-acting barbiturate methohexital (100 microg/kg/injection) during daily 1-hour sessions under a fixed-ratio 10, 60 s time-out, schedule of i.v. drug injection. This dose of methohexital maintained high rates of responding averaging 0.9 responses per second. Midazolam was then substituted for methohexital, and midazolam dose was subsequently varied from 0.3 to 3 microg/kg/injection. Each dose of midazolam was tested for five consecutive sessions and each unit dose condition was separated by five sessions of vehicle extinction. The midazolam dose-response function was an inverted U-shaped curve, with maximal rates of self-administration responding averaging 1.01 responses/second at a dose of 1 microg/kg/injection (an average of 48 injections per 1-hour session). The rates and fixed-ratio patterns of responding maintained by self-administration of midazolam in the present study were comparable to the rates and patterns of responding maintained in squirrel monkeys by self-administration of other drugs of abuse, including cocaine, amphetamine, nicotine and tetrahydrocannabinol, under similar experimental conditions.

Animals↗

PubMed1976

Role of noradrenergic and dopaminergic processes in amphetamine self-administration.

Dogs were trained to intravenously self-administered d-amphetamine (0.05 mg/kg/infusion) until a stable intake per 4 hr daily session was achieved. When the dogs were given noncontingent infusions of d-amphetamine in varying amounts o% to 100% of the baseline intake) immediately prior to the session, they decreased their self-administration response rate appropriately so that total drug intake remained constant. However, there were not changes in subsequent responding for d-amphetamine following pretreatment with either the noradrenergic agonist methoxamine (0.5-2.0 mg/kg) or the noradrenergic antagonist phenoxybenzamine (1-8 mg/kg). Additionally, responding was not maintained when methoxamine (0.05 mg/kg/infusion) was substituted for d-amphetamine. In contrast, pretreatment with either the dopaminergic antagonist pimozide (5-40 mug/kg) or chlorpromazine (0.25-2.0 mg/kg) produced dose-dependent increases in the number of self-administered d-amphetemine infustions. These data suggest that noradrenergic neurotransmission is not responsible for d-amphetamine self-administration, but an intact dopaminergic system does appear to be important.

Animals↗

PubMed1983

Oral self-administration of methohexital in baboons.

Oral self-administration of methohexital was generated in baboons that were food-restricted but not water-deprived. Stable intake of an 8% ethanol solution (two baboons) or water (two baboons) was first established in 3-h-sessions. Increasing concentrations of methohexital (0.005-10 mg/ml) then were substituted with a return to the ethanol or water baseline condition between methohexital conditions. For one baboon in the ethanol baseline condition, drinking was initially suppressed by methohexital substitution, but increased under a food-induced drinking procedure. For all baboons, an inverted U-shaped function generally described the relation between methohexital concentration and volume consumed. Anesthetization was observed at concentrations of 1.6 mg/ml and above. In two-bottle choice tests, three baboons generally drank greater volumes of methohexital than water at concentrations of 0.8 mg/ml and above. After a methohexital-free period of 1-3 months methohexital self-administration was readily reestablished.

Animals↗