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PubMed1993

The effects of nalbuphine and butorphanol treatment on cocaine and food self-administration by rhesus monkeys.

This study was designed to determine whether opioid mixed agonist-antagonist analgesics other than buprenorphine also selectively reduce cocaine self-administration by rhesus monkeys. The effects of daily treatment with nalbuphine (0.1 to 3 mg/kg/day) or (0.254 to 7.62 mumol/kg/day), butorphanol (0.01 to 0.3 mg/kg/day) or (0.0209 to 0.628 mumol/kg/day), and saline on cocaine and food self-administration were each studied for 40 sessions over 10 consecutive days. Cocaine (0.05 or 0.10 mg/kg/inj) and food (1-gm banana pellets) self-administration were maintained on a fixed ratio 4 (variable ratio 16:S) schedule of reinforcement. Both nalbuphine and butorphanol reduced cocaine self-administration (p < 0.0001) but this effect was not selective since food self-administration also decreased in a dose-dependent manner (p < 0.0001). Nalbuphine administration (1 to 3 mg/kg/day) decreased cocaine injections to 40% to 60% below baseline (p < 0.01) and food pellets 30% to 68% below baseline (p < 0.01). Lower doses of nalbuphine (0.10 and 0.30 mg/kg) did not change cocaine- or food-maintained responding significantly. All doses of butorphanol (0.01 to 0.3 mg/kg/day) reduced cocaine injections to 16% to 58% below baseline (p < 0.01). Food self-administration decreased to 21% to 70% below baseline (p < 0.01) at butorphanol doses of 0.03 to 0.3 mg/kg/day). These data suggest that these opioid mixed agonist-antagonist analgesics may not be useful as pharmacotherapies for the treatment of cocaine abuse.

Analysis of Variance↗

PubMed2002

The pharmacokinetic determinants of the frequency and pattern of intravenous cocaine self-administration in rats by pharmacokinetic modeling.

We investigated the pharmacokinetic determinants of the frequency of intravenous cocaine self-administration in 2.5-h sessions. Two groups of rats were implanted with dual catheters that permitted cocaine infusion and blood sampling via the femoral and jugular vein catheters, respectively. Half of the animals in each group self-administered one of the two cocaine unit doses (0.5 and 1 mg/kg/infusion) by pressing a lever under a continuous schedule of reinforcement. To monitor serum cocaine concentrations, the remaining animals received concurrent, response-independent infusions whenever the matched animals self-administered cocaine infusions. Multiple concentration-time data in two successive self-administrations were determined to monitor the extent of fluctuation in concentrations by pharmacokinetic modeling. Behavioral analyses revealed the higher unit dose (1 mg/kg) resulted in less frequent cocaine self-administration, and a longer interinfusion interval, whereas the total doses were similar for the two groups (24.5-27.0 mg/kg/2.5 h). Cocaine decayed biexponentially. Both the values of clearance and terminal elimination rate constant for the self-administration paradigm were significantly greater than those after the bolus cocaine dosing series (0.5 and 1 mg/kg, separated by 3 days). The regularity in cocaine self-administration produced relatively stable serum cocaine concentrations that oscillated between maximum (C(max)) and minimum (C(min)) values regardless of dose size and interinfusion interval. Although the C(max) for the 1-mg/kg unit dose (1.47 microg/ml) was significantly higher than that for the 0.5-mg/kg dose (0.82 microg/ml), the C(min) values between the groups approximated each other (0.28, and 0.34 microg/ml, respectively). Hence, the C(min) is the determinant of the initiation of the next drug-taking behavior.

Animals↗

PubMed2001

Exposure to novel environmental stimuli decreases amphetamine self-administration in rats.

Researchers examined whether exposure to novel environmental stimuli reduces drug self-administration. Rats were trained to self-administer amphetamine on a fixed ratio (FR) 5 schedule of reinforcement and then were exposed to novel stimuli during the session. Responding was significantly decreased with exposure to novelty but returned to baseline levels on intervening nonexposure sessions. In 2 subsequent experiments, rats were exposed to novel plastic objects prior to the session. Immediately following exposure, rats were allowed to self-administer amphetamine on an FR 1 schedule, which was increased gradually to an FR 5 either using predetermined increments or on the basis of performance criteria. Exposure to the novel objects significantly decreased acquisition of amphetamine self-administration in both situations. Results suggest that exposure to novel environmental stimuli may be effective at reducing drug self-administration.

Amphetamine↗

PubMed2003

Accumbal neural responses during the initiation and maintenance of intravenous cocaine self-administration.

During a chronic extracellular recording session, animals with a history of cocaine self-administration were allowed to initiate drug seeking under drug-free conditions. Later, in the same recording session, animals engaged in intravenous cocaine self-administration. During the drug-free period, 31% of 70 accumbal neurons showed a significant increase in average firing rate in association with either or both the exposure to cues that signaled the onset of cocaine availability and the subsequent onset of drug-seeking behavior. The neurons that showed an average excitatory response during the drug-free period were the only group of neurons that showed an average excitatory phasic response to cocaine-reinforced lever presses during the drug self-administration session. A majority of the neurons that were activated during the drug-free period, like the majority of other neurons, showed decreases in average firing in response to self-administered cocaine. However, the neurons that were activated during the drug-free period maintained a higher rate of firing throughout the self-administration session than did other accumbal neurons. The data of the present study are consistent with the conclusion that accumbal neurons contribute to, or otherwise process, initiation of drug seeking under drug-free conditions and that they do so via primarily excitatory responses. Furthermore, there is continuity between the drug-free and -exposed conditions in neural responses associated with drug seeking. Finally, the data have potential implications for understanding mechanisms that transduce accumbal-mediated drug effects that contribute to drug addiction.

Action Potentials↗

PubMed1977

On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine.

The role of ascending noradrenergic (NA) and dopaminergic (DA) systems in intravenous self-administration of cocaine in rats was investigated by examining the effects of 6-hydroxydopamine-induced lesions of these systems on responding for the drug on a FR-1 schedule of reinforcement. Lesions of the dorsal and ventral NA bundles that reduced hippocampal-cortical NA by 96% and hypothalamic NA by 72% failed to have any effects on responding for cocaine. Lesions of the nucleus accumbens that reduced the DA content of this nucleus by 90% resulted in a significant and long-lasting (15 days) reduction in self-administration of cocaine. Apomorphine self-administration was not affected in the same animals. Identical lesions of the n accumbens had only transient (2-3 days) effects on food-reinforced operant responding, suggesting that the prolonged disruption of cocaine self-administration was not the result of motor deficits. The results are discussed with reference to the possibility that DA terminals in the n accumbens may mediate some of the positive reinforcing properties of cocaine.

Animals↗

PubMed2003

Extinction of cocaine self-administration produces alterations in corticotropin releasing factor gene expression in the paraventricular nucleus of the hypothalamus.

The long-term effect of cocaine self-administration on corticotropin releasing factor (CRF) mRNA content in the hypothalamic CRF-containing neurons has not yet been established. The purpose of this study was to examine the time course effects of the extinction of cocaine self-administration behavior on CRF gene expression in the paraventricular nucleus of the hypothalamus (PVN) using in situ hybridization histochemistry (IHHS). Seventy-two littermate male Lewis rats were randomly assigned in triads to one of three conditions: (a) contingent intravenous self-administration of 1 mg/kg/injection of cocaine (CONT), (b) non-contingent injections of either 1 mg/kg/injection of cocaine (NONCONT) or (c) saline yoked (SALINE) to the intake of the self-administering subject. The self-administering rats were trained to self-administer cocaine under a fixed ratio 5 (FR5) schedule of reinforcement for a minimum of 3 weeks. After stable baseline levels of drug intake had been reached, saline was substituted for drug. Following this first extinction period, cocaine self-administration was reinstated for an additional period of 2 weeks. Immediately after cessation of the last session of cocaine self-administration (Day 0) and 1, 5 and 10 days after the second extinction period, animal brains in each triad were removed to be processed for IHHS. CRF mRNA levels in the PVN were significantly lower in the NONCONT cocaine group at Day 0 compared to CONT or SALINE groups. On Day 1, hypothalamic CRF gene expression significantly decreased in the CONT cocaine group with respect to the SALINE group, but there were no differences between the cocaine groups or among the NONCONT cocaine and SALINE groups. After 5 and 10 days of extinction, no differences were found in CRF mRNA content in the PVN between the three conditions of this study. These results suggest that, after the extinction of cocaine self-administration, changes in hypothalamic CRF gene expression are differentially affected depending upon the type of cocaine administration, and that the stages of cocaine withdrawal might not be associated with enduring changes in hypothalamic CRF mRNA levels.

Analysis of Variance↗

PubMed2002

Rat strain differences in nicotine self-administration using an unlimited access paradigm.

An effective animal model for elucidating the neurobiological basis of human smoking should simulate important aspects of this behavior. Therefore, a 23 h unlimited access nicotine self-administration model was used to compare inbred Lewis rats, which have a propensity to self-administer drugs of abuse, to inbred Fisher 344 rats and to the outbred Holtzman strain. Using this unlimited access model, 88.8% of Lewis vs. 57.1% of Holtzman rats achieved maintenance self-administration at a fixed ratio 1 (FR 1) at 0.03 mg/kg IV nicotine (P<0.05). In contrast, Fisher rats did not acquire self-administration under these conditions. Of the Lewis and Holtzman rats that achieved maintenance self-administration on an FR 1 schedule, a greater percentage of Lewis rats acquired nicotine self-administration at FR 2 (P<0.05) and progressed to FR 4 (P<0.05). Using naïve cohorts in a progressive dose reduction study, 83.3% of Lewis rats achieved maintenance at 0.0075 mg/kg nicotine as compared to 31.8% of Holtzman rats (P<0.05). Furthermore, only Lewis rats showed differences in active vs. inactive bar presses during maintenance at sequential dose reductions (P<0.001). Thus, in this unlimited access model, inbred Lewis rats will more reliably acquire nicotine self-administration than outbred Holtzman rats. Moreover, Lewis rats showed a significantly higher likelihood of continuing to self-administer nicotine in face of both increasing work requirements and decreasing drug reinforcement. Therefore, it is likely that Lewis rats would be genetically susceptible to nicotine addiction.

Animals↗

PubMed1980

Effects of heroin self-administration on cigarette smoking.

Cigarette smoking increased during heroin self-administration in comparison to drug-free and methadone detoxification conditions in eight heroin addicts given naltrexone placebo (P less than 0.01) and three heroin addicts given buprenorphine placebo. Cigarette smoking was stable across conditions for one subject who did not use heroin during naltrexone blockade of heroin effects. Five subjects smoked significantly more (P less than 0.01) during the hour following a heroin injection than during the preceding hour, and two subjects in the same group smoked significantly less following a heroin injection (P less than 0.05). Subjects smoked significantly more during the evening and night when self-administering heroin than during baseline conditions (P less than 0.05), but subjects did not sleep significantly less during heroin self-administration. The peak of the intercigarette interval distribution remained between 16-30 min during baseline and heroin conditions. However, the increased smoking during heroin use appeared to reflect a higher rate of smoking rather than a generalized increase across intercigarette intervals. These data extend previous findings, that alcohol consumption is associated with increased cigarette smoking, to IV heroin self-administration.

Adult↗

PubMed2004

The effect of novelty on amphetamine self-administration in rats classified as high and low responders.

RATIONALE: Rats categorized as high responders (HR) based on their activity in an inescapable novel environment self-administer more amphetamine than low responder (LR) rats. Previous research has also demonstrated that novel stimuli presented during the amphetamine self-administration session decreases the number of infusions earned. OBJECTIVES: This study determined whether individual differences in response to inescapable or free-choice novelty differentially predict the ability of novel stimuli to decrease amphetamine self-administration. Further, this study determined whether novel stimuli maintained the ability to reduce self-administration with repeated presentations, and whether the effect of novel stimuli varied as a function of the unit dose of amphetamine tested. METHODS: Male rats were screened for their response in inescapable and free-choice novelty tests. Following initial training using a high unit dose of amphetamine (0.1 mg/kg per infusion), the dose was reduced (0.03 mg/kg per infusion), and novel stimuli were presented in the operant conditioning chamber on four separate sessions. In experiment 2, novel stimuli were presented during several sessions at a variety of amphetamine doses (0.003, 0.01, 0.03, and 0.056 mg/kg per infusion). RESULTS: Four repeated presentations of novel stimuli reduced amphetamine self-administration with no significant loss in the effect of novel stimuli across repeated presentations. In experiment 2, novel stimuli reduced amphetamine self-administration at low unit doses (0.003 mg/kg and 0.01 mg/kg per infusion), and rats classified as HR based on their activity in inescapable novel stimuli were more disrupted by novel stimuli than LR rats. CONCLUSIONS: These results suggest that repeated presentation of novel stimuli can reduce amphetamine self-administration at low unit doses and that HR rats are more sensitive than LR rats to non-drug stimuli that compete with responding for amphetamine.

Amphetamine↗

PubMed1993

EEG changes with different levels of morphine self-administration.

Rats with chronically implanted jugular catheters and cortical EEG electrodes were allowed 24 hr per day access to morphine infusions (30 micrograms/kg) contingent on lever-pressing. Yoked control subjects received the same number and pattern of infusions as contingent subjects in an adjacent cage. Six subjects were studied, with data analyzed over 84 days of contingent and 63 days of yoked control (noncontingent) treatment. Self-administration rates were positively correlated with previous exposure to morphine. EEG total power was reduced in both contingent and yoked subjects during periods of self-administration. Averaging of trends in EEG power over time across multiple episodes of self-administration showed a greater reduction in power for contingent subjects that preceded the majority of morphine infusions. Desynchronization (diminished EEG amplitude) for contingent subjects at the onset of self-administration is probably related to lever-pressing activity. Ultradian describes biological rhythms in which the duration of one cycle (period) ranges from several minutes to values less than 24 hr. In both contingent and yoked subjects at intermediate or high levels of self-administration, increases occurred in the period and amplitude of ultradian cycles in EEG total power. Responsiveness to the light-dark cycle was also diminished at these levels of self-administration. In conclusion, morphine self-administration at intermediate or high levels disrupts both diurnal and ultradian rhythms in EEG total power for both contingent and yoked subjects. The ultradian EEG pattern associated with greater levels of morphine self-administration resembles diminished variation in EEG power that occurs normally during the inactive rest phase of the diurnal cycle.

Analysis of Variance↗

PubMed1993

Emotional but not physical stress enhances intravenous cocaine self-administration in drug-naive rats.

Involvement of stress in the etiology of drug dependence has received little attention. In the present study a number of behavioural manipulations were applied and examined for an effect on intravenous cocaine self-administration in drug-naive rats with no prior training in leverpress responding. Self-administration rate was measured during five consecutive daily sessions. Stress reduction by handling rats daily for two weeks prior to testing for self-administration did not affect cocaine self-administration. Acute physical stress was induced either by a hot plate or by repeated footshocks, and emotional stress was induced by forcing rats to witness another rat being subjected to repeated footshocks. These stressors were applied immediately prior to each cocaine self-administration session. Emotional but not physical stress enhanced the rate of cocaine self-administration. It is concluded that emotional distress may increase the rewarding effects of cocaine and may render an individual more susceptible to development of drug dependence.

Animals↗

PubMed1998

The effects of buprenorphine on self-administration of cocaine and heroin "speedball" combinations and heroin alone by rhesus monkeys.

Concurrent abuse of cocaine and opioids is frequently observed clinically, and we have developed a model of "speedball" self-administration involving the simultaneous injection of cocaine and heroin combinations in rhesus monkeys (Mello et al. (1995) J Pharmacol Exp Ther 274:1325). In the present study, we evaluated the effects of buprenorphine (0.0075-0.75 mg/kg/day i.v.) and saline on speedball combinations of cocaine [0.001, 0.01 or 0.10 mg/kg/inj] and heroin [0.0001-0.032 mg/kg/inj]. We also examined the effects of buprenorphine (0.075 and 0.237 mg/kg/day i.v.) on self-administration of heroin alone (0.0001-0.01 mg/kg/inj). Drug and food (1-g banana pellets) self-administration were maintained on a second-order FR4 (VR16:S) schedule in four 1-hr sessions each day. Each buprenorphine or saline control treatment was evaluated for 10 consecutive days, and monkeys returned to base-line performance between each treatment condition. Buprenorphine (0.075-0.75 mg/kg/day) selectively reduced self-administration of speedball combinations of low-dose cocaine (0.001 mg/kg/inj) and heroin (0.001 or 0.0032 mg/kg/inj) (P < .05-.01), and buprenorphine (0.237 mg/kg/day) shifted dose-effect curves for speedball combinations of cocaine (0.001 mg/kg/inj) and heroin (0.0001-0.032 mg/kg/inj) downward (P < .05-.01) and approximately 1 log unit to the right. Buprenorphine treatment was less effective in decreasing responding maintained by speedball combinations of heroin and 0.01 and 0.10 mg/kg/inj cocaine. Buprenorphine treatment (0.075 and 0.237 mg/kg/day) also shifted the heroin dose-effect curve downward (P < .01-.001) and to the right. Both speedball and heroin self-administration were associated with dose-dependent decreases in food-maintained responding during saline control treatment. However, food-maintained responding was often higher than control levels during buprenorphine treatment (P < .05-.001), which suggests that buprenorphine antagonized the rate-decreasing effects of speedballs and of heroin. Buprenorphine's selective reduction of speedball and heroin self-administration is consistent with clinical treatment trials in opioid abusers and polydrug abusers. Thus, these primate models of speedball and heroin self-administration should be useful for preclinical evaluation of novel drug abuse treatment medications.

Animals↗

PubMed1997

Factors influencing marijuana self-administration by humans.

The self-administration of marijuana cigarettes varying in tetrahydrocannabinol (THC) content was measured by having participants choose between marijuana and an alternative reinforcer, i.e., snack food. Twelve marijuana users (eight men, four women), in groups of four, participated in a 16-day residential study. Each day, participants had the opportunity to choose repeatedly between a marijuana cigarette and a snack. The THC concentration of the cigarette changed each day (0.0, 2.2 or 3.9% delta 9-THC w/w), as did the number of snack items (one or two); each THC concentration was compared to each snack condition twice. Days were divided into a work period (09.15-16.45 h), comprising performance and subjective-effects tasks, and a recreation period (17.15-23.30 h). Each day at 10.00 h, participants "sampled" a marijuana cigarette containing the delta 9-THC concentration available that day, and selected the number of snack items available that day. Six "choice" trials occurred from 14.00-19.00 h, when participants responded under a modified progressive ratio schedule for either marijuana or snacks. At 18.15 h, participants could participate in a 10-min math task, in which each correct answer earned $1.00. Cigarettes containing 2.2 or 3.9% delta 9-THC were self-administered more often than placebo. The only other factor influencing marijuana choice was the opportunity to earn additional money, with participants choosing not to smoke immediately before the math task. By the end of the study, active marijuana had smaller effects on ratings of "high", "stimulated," and "good drug effect." These data demonstrate that: (a) delta 9-THC is an essential reinforcing component of marijuana; (b) marijuana use may be manipulated by monetary contingencies; and (c) tolerance may develop more readily to marijuana's subjective effects than its reinforcing effects.

Adult↗

PubMed2001

Comparative effects of dextromethorphan and dextrorphan on morphine, methamphetamine, and nicotine self-administration in rats.

The effects of dextromethorphan and its metabolite dextrorphan on morphine, methamphetamine and nicotine self-administration and on responding for a nondrug reinforcer (water) were assessed in rats. Both dextromethorphan and dextrorphan decreased morphine self-administration at 10-30 mg/kg, s.c., decreased methamphetamine self-administration at 20 and 30 mg/kg, s.c., and decreased nicotine self-administration at 5-30 mg/kg, s.c.; doses of both drugs less than 40 mg/kg, s.c. did not affect responding for water. The equal potencies of dextromethorphan and dextrorphan suggest mediation of these effects by a non-NMDA receptor mechanism, possibly involving blockade of alpha3beta4 nicotinic receptors. The results also suggest that dextromethorphan should be tested extensively as a potential treatment for diverse populations of drug-abusing patients.

Analgesics, Opioid↗

PubMed2006

Escalation of i.v. cocaine self-administration and reinstatement of cocaine-seeking behavior in rats bred for high and low saccharin intake.

RATIONALE: Rats selectively bred for high saccharin (HiS) intake consume more alcohol, acquire intravenous (i.v.) cocaine self-administration more rapidly, and show more dysregulated patterns of cocaine self-administration than their low saccharin-consuming (LoS) counterparts. OBJECTIVES: The purpose of the present study was to determine whether HiS and LoS rats also differ in the escalation, maintenance, extinction, and reinstatement of i.v. cocaine self-administration. MATERIALS AND METHODS: Two experiments were conducted in separate groups of rats. In the first experiment, HiS and LoS female rats were allowed to self-administer cocaine [0.4 mg/kg; fixed ratio (FR) 1] under short (ShA, 2 h per day) or long (LgA, 12 h per day) access conditions for 21 days. Session lengths were subsequently equated (2 h), and FR1-maintained cocaine self-administration was examined. In the second experiment, additional groups of HiS and LoS female rats were given access to cocaine (0.4 mg/kg; FR 1) self-administration during 2-h sessions for 10 days. Subsequently, saline was substituted for cocaine, and responding was extinguished. After a 14-day extinction period, saline- and cocaine-[5, 10, and 15 mg/kg, intraperitoneal (i.p.)] induced reinstatement of drug-seeking behavior was measured. RESULTS: HiS LgA rats escalated their cocaine intake more rapidly than LoS rats, and during the 2 h sessions after escalation cocaine self-administration was significantly higher in HiS LgA rats, compared to LoS LgA rats. HiS rats responded on the cocaine-paired lever more than LoS rats during maintenance, extinction, and cocaine-(15 mg/kg) induced reinstatement. CONCLUSIONS: These results suggest that HiS and LoS rats have distinct drug-seeking and drug-taking profiles. The HiS and LoS rats differ along a wide range of behavioral dimensions and represent an important model to study the interactions of excessive intake of dietary substances and vulnerability to drug abuse.

Animals↗

PubMed1987

Microinjection of oxytocin into limbic-mesolimbic brain structures disrupts heroin self-administration behavior: a receptor-mediated event?

The systemic injection of oxytocin (OXT) decreases the self-administration of heroin in heroin-tolerant rats. Since OXT-ergic binding sites are present in limbic and mesolimbic brain regions, the effects of intracerebral microinjections of OXT were investigated. In heroin-tolerant rats, the microinjection of OXT (2 ng) into the anterodorsal part of the nucleus accumbens or into the ventral hippocampus disrupted the self-administration of heroin. The effect of intrahippocampal microinjections lasted longer than that of intraaccumbens injections. The administration of N alpha-acetyl-(2-0-methyltyrosine)-oxytocin (ACME-OXT), an inhibitor of oxytocin receptors, prevented the disruptive effect of intrahippocampal OXT injections on heroin self-administration. It is concluded that limbic-mesolimbic brain structures have an essential role in the expression of the disruptive action of OXT on heroin self-administration. It appears that OXT-ergic binding sites mediate the effects of OXT.

Animals↗

PubMed2002

Nighttime versus daytime hypnotic self-administration.

RATIONALE AND OBJECTIVES: Previous studies have shown that insomniacs self-administer hypnotics at high nightly rates. This study assessed whether insomniacs' self-administration of hypnotics extended to the daytime. METHODS: Forty-four healthy men and women, 21-55 years old, with ( n=22) and without ( n=22) insomnia volunteered. They were randomized to one of two triazolam dose groups (0.125 or 0.25 mg) and their preference for placebo versus triazolam was assessed at night (2300 hours) and day (0900 hours) over 7 consecutive days in each phase. In both night and day phases of the study, subjects received triazolam or placebo in color-coded capsules on two sampling days or nights and then were forced to choose their preferred capsule on 5 subsequent days or nights. The order of day and night study phases and the placebo and triazolam sampling days was counterbalanced. In the night phase subjects went to bed from 2330 to 0730 hours and in the day phase they were tested for level of sleepiness-alertness at 1000, 1200, 1400, and 1600 hours by the multiple sleep latency test (MSLT) and mood and performance at 1100 and 1500 hours. RESULTS: More triazolam was chosen at night than during the day. No dose differences in preferences at night versus day or between insomniacs and normals were found. Insomniacs did not differ in their triazolam preferences between night and day, while the normals chose triazolam less frequently during the day. Among insomniacs, 40% chose triazolam on >3 of the 5 days. On both screening and placebo sampling days, those with a high (>60%) daytime triazolam preference had greater average daily sleep latencies on the MSLT than those with a low (<50%) daytime triazolam preference (i.e. with a placebo preference). In the triazolam preference group, triazolam reduced daily MSLT latencies to the level of the placebo preference group. CONCLUSIONS: This study shows that the minority of insomniacs who self-administer hypnotics during the day are physiologically aroused and the drug reduces their arousal suggesting that their daytime self-administration, like their night-time self-administration, is more consistent with therapy-seeking than drug-seeking behavior, at least for the short-term.

Adult↗

PubMed2000

18-MC reduces methamphetamine and nicotine self-administration in rats.

In previous studies, 18-methoxycoronaridine (18-MC), a novel iboga alkaloid congener, has been found to decrease the intravenous self-administration of morphine and cocaine in rats. In the present study, 18-MC (1-40 mg/kg, i.p.) dose-dependently decreased the i.v. self-administration of methamphetamine and nicotine. As in the previous studies, drug self-administration was reduced for > or = 24 h after the highest dose of 18-MC. A comparison of 18-MC's interactions with all four drugs of abuse studied so far indicated that 18-MC is least effective in decreasing methamphetamine self-administration and most potent in decreasing nicotine self-administration. The results suggest that a nicotinic antagonist action of 18-MC contributes to its putative anti-addictive efficacy.

Animals↗