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PubMed1995

Diurnal patterns of cocaine and heroin self-administration in rhesus monkeys responding under a schedule of multiple daily sessions.

A number of non-pharmacological factors have been shown to influence drug self-administration in experimental animals. This report examines diurnal changes in drug self-administration by rhesus monkeys trained to self-administer food (1gm fruit-flavored pellets) and cocaine (0.01 or 0.032mg/kg/injection) under a second order FR4 (VR16:S) schedule during four daily food and drug self-administration sessions. Saline, different unit doses of cocaine (0.001-0.1mg/kg/injection) or different unit doses of heroin (0.0001-0.01mg/kg/injection) were substituted for the maintenance dose of cocaine during drug sessions. Dose-effect curves relating unit dose of cocaine or heroin to the number of injections per session displayed an inverted U-shape during each of the four daily drug sessions. When 0.032mg/kg/injection cocaine or 0.0032mg/kg/injection heroin were available, monkeys usually self-administered the maximum number of injections during all four drug sessions. Substitution of saline or lower unit doses of cocaine (0.001-0.01mg/kg/injection) or heroin (0.0001-0.001mg/kg/injection) decreased the number of injections/session; however, these decreases were consistently greater during the evening (20.00-21.00h) and morning (07.00-08.00h) sessions than during the afternoon sessions (12.00-13.00h and 16.00-17.00h). As a result, the ascending limbs of the cocaine and heroin dose-effect curves for the evening and morning sessions were shifted to the right of the ascending limbs of the dose-effect curves for the afternoon sessions. Moreover, when saline was substituted for cocaine for only two sessions per day, drug self-administration decreased more during the evening and morning sessions even when the cocaine was available during those sessions. These findings suggest a diurnal variation in cocaine and heroin self-administration. Specifically, drug self-administration during the evening and morning sessions appears to be more sensitive to a decrease in reinforcer magnitude than responding during the afternoon sessions. These findings confirm and extend previous reports of the influence of non-pharmacological factors on drug self-administration.

Journal Article↗

PubMed2006

The nociceptin/orphanin FQ receptor agonist Ro 64-6198 reduces alcohol self-administration and prevents relapse-like alcohol drinking.

Effects of the opioid receptor like-1 (ORL-1) receptor agonist Ro 64-6198 (0.1, 0.3, and 1.0 mg/kg intraperitoneally (i.p.)) on operant ethanol self-administration and activation of self-administration by ethanol deprivation were studied in male Wistar rats. Acute administration of Ro 64-6198 caused a dose-dependent reduction of ethanol self-administration. In comparison, the opioid antagonist naltrexone (0.1, 0.3, and 1.0 mg/kg i.p.) inhibited ethanol self-administration at all doses tested. Ethanol deprivation for 10 days significantly increased ethanol self-administration during the first 2 days after deprivation. Daily pretreatment with Ro 64-6198 (0.3 mg/kg) or naltrexone (0.3 mg/kg) during the last 3 days of ethanol deprivation abolished the deprivation-induced increase in ethanol intake. Thus, stimulation of the ORL-1 receptors by Ro 64-6198 reduced the acute reinforcing effects of ethanol and prevented relapse-like behavior in the ethanol-deprivation model in a similar manner as a blockade of opioid receptors by naltrexone. Ro 64-6198 at 0.1 and 0.3 mg/kg doses did not alter self-administration of 0.2% saccharin solution, indicating an apparent selectivity of this compound in modification of ethanol reward. These findings add further support to the idea that Ro 64-6198 and potentially other synthetic ORL-1 receptor agonists are as effective as naltrexone in blocking the actions of ethanol important for its addictive potential in animal experiments, and therefore may have therapeutic value in the treatment of alcoholism.

Alcohol Drinking↗

PubMed1997

Cocaine self-administration in ovariectomized rats is predicted by response to novelty, attenuated by 17-beta estradiol, and associated with abnormal vaginal cytology.

Parameters of cocaine self-administration behavior and vaginal cytological changes were assessed in ovariectomized rats during and after chronic self-administration. Response to novelty as measured by locomotor activity was found to correlate with cocaine self-administration on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. Chronic 17-beta estradiol (E2) replacement did not affect cocaine self-administration on FR or PR schedules of reinforcement. Acute E2 administration decreased cocaine self-administration on a PR schedule of reinforcement on the day of and on the two days following hormone treatment. Finally, the proliferation of vaginal epithelia following acute E2 was potentiated in rats both during cocaine self-administration and 30 days into withdrawal when compared with non-drug-exposed animals. These results identify response to novelty as a behavioral index predictive of cocaine self-administration liability in female rats and additionally provide evidence of psychostimulant-hormonal interactions highly relevant to female behavior and physiology.

Animals↗

PubMed1978

Continuous intravenous naltrexone effects on morphine self-administration in rhesus monkeys.

Rhesus monkeys, surgically prepared with intravenous catheters, were given opportunities to self-administer morphine for 3 days, methamphetamine for 2 days and saline for 2 days in a constantly repeating cycle. Access to drugs was limited to a 15-minute period every 4 hours. After stable base-line self-administration rates, saline or various concentrations of naltrexone were infused continuously through the catheter. In the first phase of the study each concentration of naltrexone was infused for 4 weeks (separated by 3 weeks of saline) while the dose of morphine available for self-administration was held constant at 8 microgram/kg/injection. Stable naltrexone dose-related suppression of morphine self-administration occurred throughout each 4-week infusion. In the second phase of the study, various doses of morphine were made available for self-administration during 6- to 8-week continuous infusions of saline or various concentrations of naltrexone. The dose-effect curve relating self-administration rate to morphine dose per injection shifted to the right and decreased in maximum as the rate of infusion of naltrexone increased. Methamphetamine and saline self-administration rates were unaffected by naltrexone.

Animals↗

PubMed2004

Sex differences in the escalation of intravenous cocaine intake following long- or short-access to cocaine self-administration.

Preclinical data have indicated that extended access to cocaine self-administration (e.g., 6-12 h/day) facilitates an escalation in daily cocaine intake that is not seen when rats are given shorter (e.g., 1-2 h/day) access to cocaine for self-administration. Data from studies with rats have shown that females self-administer more cocaine than males during all phases of drug abuse (e.g., acquisition, maintenance, and reinstatement). The purpose of this study was to examine potential differences between males and females in the escalation of intravenous cocaine intake following a differential access (e.g., 1 vs. 6 h) period of cocaine self-administration. Four groups of rats were compared: (1) long-access (LgA; 6 h) females; (2) LgA males; (3) short-access (ShA; 1 h) females; and (4) ShA males. Animals were given LgA or ShA to intravenous cocaine (0.5 mg/kg/infusion) self-administration under an Fr 1 schedule for 21 days. Subsequently, access conditions were made equal (3 h) across groups, and dose-response curves for cocaine were compared. Results revealed that the LgA groups' dose-response curves were significantly elevated above those of ShA groups. Additionally, the dose-response curve of LgA female rats was significantly elevated above that of LgA male rats. These results suggest that female rats are more sensitive than male rats to factors that contribute to the escalation of cocaine intake (e.g., extended access conditions).

Animals↗

PubMed2003

Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration.

We characterized spontaneous and mecamylamine-precipitated nicotine withdrawal using intravenous nicotine self-administration, the acoustic startle response, prepulse inhibition and somatic signs of withdrawal in DBA/2J mice. Nicotine dependence was induced by continuous nicotine infusion through osmotic minipumps. Nicotine self-administration was studied before and after the induction of dependence. The initial test revealed significant nicotine self-administration at the 0.048 microg/infusion dose. During the second self-administration test, saline-treated mice exhibited increased aversiveness of response-contingent infusions of high nicotine doses; these changes were not seen in the nicotine-treated animals reflecting tolerance to nicotine's effects. Neither mecamylamine administration nor spontaneous withdrawal affected the expression of somatic signs, except that increases in jumping were observed during spontaneous withdrawal. Finally, nicotine withdrawal increased general activity in the startle chambers when no stimuli were presented, possibly reflecting increased body tremor and/or agitation, and decreased prepulse inhibition reflecting a sensorimotor gating deficit; the last two effects were reversed by nicotine self-administration. Thus, nicotine withdrawal results in modest, but yet detectable, changes in the behavior of mice.

Animals↗

PubMed2007

Effects of dose and session duration on cocaine self-administration in rats.

Previous studies showed that an extended 6-h session duration produced an increasing rate of cocaine self-administration in rats. The present study further investigated the effect of dose and session duration on cocaine self-administration. Eight groups of rats (4 doses x 2 session durations) self-administered one of four cocaine doses (0.25, 0.5, 1, and 2 mg/kg/injection) in either 1- or 6-h sessions under a fixed-ratio schedule. In another experiment, two other groups of rats self-administered 0.5 mg/kg/injection of cocaine in either 3- or 12-h sessions. Cocaine self-administration increased at all doses in 6-h sessions but not in 1-h sessions. Cocaine intake (milligram/kilogram) reached an asymptote earlier at a higher dose, but the rate of responding increased faster when the dose was lower. In ShA rats, the cocaine dose-response function was higher in rats at the two higher unit doses than at the lower doses. Cocaine self-administration increased in 6- and 12-h sessions, but not in 1- and 3-h sessions. The increase in self-administration was faster and greater in 12-h sessions than 6-h sessions. The data suggest that cocaine self-administration increases at various doses with prolonged access and that an increase in the rate of responding is positively and inversely associated with session duration and unit dose, respectively. Results also imply that cocaine intake reaches a ceiling faster at high doses even under short session duration. Therefore, high doses or prolonged access to cocaine are more likely to result in a pattern of cocaine intake that reflects compulsive use.

Animals↗

PubMed1995

Pretreatment with the dopamine agonist 7-OH-DPAT shifts the cocaine self-administration dose-effect function to the left under different schedules in the rat.

This study tested the hypothesis that administration of the dopamine agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) shifts the cocaine self-administration dose-effect function to the left, rather than producing nonspecific effects or exclusively enhancing the rate-decreasing effects of high doses of cocaine. Under fixed-ratio or progressive-ratio schedules, rats were allowed to intravenously self-administer cocaine, 7-OH-DPAT, or a combination of cocaine and 7-OH-DPAT. In additional tests under fixed-ratio schedules, cocaine self-administration followed subcutaneous pretreatment with 7-OH-DPAT. Cocaine dose-effect functions were obtained by varying the unit dose of cocaine either between test sessions or within a single session. Intravenous 7-OH-DPAT (1-4µg) decreased self-administration of the training dose of cocaine (0.25mg) under a fixed-ratio schedule, but failed to shift the entire cocaine self-administration dose-effect function to the left under fixed-ratio or progressive-ratio schedules. 7-OH-DPAT alone maintained i.v. self-administration under these schedules, but produced a shallow self-administration dose-effect function, relative to cocaine, under the progressive-ratio schedule. In contrast to intravenous 7-OH-DPAT, s.c. pretreatment with 7-OH-DPAT (0.1-0.4mg/kg) not only decreased self-administration of the training dose of cocaine but also lowered the minimum effective dose of cocaine under fixed-ratio schedules, producing a shift to the left of the cocaine self-administration dose-effect function; these effects were independent of whether the dose of cocaine was varied between sessions or within a single session. Likewise under a multiple schedule, in which responding was maintained by cocaine and food in alternate components, s.c. pretreatment with 7-OH-DPAT increased self-administration of the dose of cocaine on the ascending limb of the dose-effect function and decreased self-administration of doses of cocaine on the descending limb, while uniformly decreasing responding for food. These observations suggest that pretreatment with 7-OH-DPAT enhances the reinforcing properties of cocaine rather than producing nonspecific effects or enhancing exclusively the rate-decreasing effects of high doses of self-administered cocaine.

Journal Article↗

PubMed1999

Sex differences in nicotine effects and self-administration: review of human and animal evidence.

Although both the human and animal literatures are notable for the general lack of attention paid to possible sex differences in drug self-administration behavior, evidence is accumulating to suggest that males and females may differ in factors that maintain tobacco smoking or nicotine self-administration. Self-administration of nicotine per se may be less robust in women, and women are less sensitive than men to some effects of nicotine that may be reinforcing. Compared to men, smoking behavior of women may be influenced more by non-nicotine stimuli associated with smoking, suggesting greater conditioned reinforcement of smoking in women. Moreover, nicotine replacement, the current standard treatment for smoking cessation, is sometimes less effective in women, further suggesting the need for greater consideration of non-nicotine factors that may maintain women's smoking. Very recent research on rats also indicates sex differences in nicotine self-administration. However, these differences are complex and suggest that nicotine-seeking behavior is composed of several components, including hedonic, incentive-motivational, and conditioning effects; males and females may differ in one or more of these components. Menstrual or estrous cycle phase effects on the maintenance of nicotine self-administration are not particularly apparent in humans or animals, although cycle phase may influence other stages of dependence (e.g., withdrawal symptoms during cessation). Future research should evaluate further the consistency of results across human and non-human species, identify the conditions and procedures under which sex differences are observed, and elucidate the specific components of reinforcement that may differ between males and females. Studies also should examine the possible generalizability of these sex differences to other drugs of abuse. Identification of specific factors responsible for these sex differences may lead to improved interventions for smoking cessation and other substance abuse in women.

Animals↗

PubMed1990

Effects of desipramine maintenance on cocaine self-administration by humans.

Six research volunteers with histories of cocaine use were tested in a cocaine choice paradigm to investigate the effects of desipramine maintenance on cocaine-taking behavior. Subjects were allowed to self-administer i.v. saline or cocaine (8, 16 or 32 mg) in daily 3-hr sessions to establish baseline levels of self-administration, self-reported effects of the drug and changes in heart rate and blood pressure. Each subject was then maintained on daily doses of desipramine for 3 to 4 weeks, after which a second cocaine self-administration dose-response curve was generated under desipramine maintenance. This maintenance had no effect on cocaine self-administration. There was, however, a significant increase in heart rate and blood pressure during desipramine maintenance. Desipramine maintenance also resulted in a change in the profile of cocaine's self-reported effects. In some cases (e.g., Arousal and Vigor on the Profile of Mood States, Benzedrine Group scale on the Addiction Research Center Inventory), reports of cocaine's effects were significantly reduced under conditions of desipramine maintenance, and in others (e.g., Anxiety, Anger and Confusion on the Profile of Mood States), those reports were significantly increased. Furthermore, there was a significant decrease in subjects response to an "I want cocaine" question while under desipramine maintenance. The data suggest that desipramine does not affect the reinforcing properties of cocaine, but may interfere with its other stimulus properties. Furthermore, the cardiovascular effects of desipramine appear to have the potential for toxicity when that drug is administered in combination with cocaine.

Adult↗

PubMed2006

Sex differences and hormonal influences on acquisition of cocaine self-administration in rats.

Men and women differ in their response to cocaine, and a woman's response varies with the menstrual cycle. For example, women have greater subjective responses to cocaine in the follicular phase of the menstrual cycle when estradiol is predominant, than they do during the luteal phase when both estradiol and progesterone are elevated. Similarly, female rats show significantly more cocaine-induced locomotor behavior and cocaine self-administration during behavioral estrus, shortly after estradiol peaks, than during other stages of the cycle, and estradiol administration to ovariectomized (OVX) females enhances the acquisition of cocaine self-administration. The purpose of this study was to expand upon these findings by studying the effects of progesterone administration to females, and estradiol administration to males, on acquisition of cocaine self-administration. We report here that there are both sex differences in and effects of circulating ovarian hormones on acquisition of cocaine self-administration. We demonstrate that although estradiol administration enhances acquisition of cocaine self-administration in OVX female rats, concurrent administration of progesterone with estradiol inhibits this effect of estradiol. In a separate experiment, we demonstrate that estradiol administration does not enhance acquisition of cocaine self-administration in castrated male rats. We conclude that (1) there is a sex difference in the effects of estradiol on cocaine self-administration: it facilitates acquisition in female, but not male rats; and that (2) in females concurrent progesterone treatment counteracts the facilitory effect of estradiol on cocaine self-administration.

Animals↗

PubMed2002

Effects of GBR 12909, WIN 35,428 and indatraline on cocaine self-administration and cocaine seeking in rats.

RATIONALE: It has been proposed that drugs that decrease cocaine self-administration or cocaine seeking by laboratory animals might be effective pharmacotherapies in the treatment of cocaine addiction. Previous studies have suggested that the dopamine uptake inhibitor, GBR 12909, might be such a candidate drug because it decreases cocaine self-administration. Other studies have shown that GBR 12909 elicits cocaine seeking, which might limit its utility as an anti-cocaine pharmacotherapy. OBJECTIVES: The present study sought to compare the potency of GBR 12909 in decreasing cocaine self-administration and in eliciting cocaine seeking. These findings were compared to effects produced by the cocaine analog, WIN 35,428 and the non-specific monoamine uptake inhibitor, indatraline. METHODS: A within-session protocol was used to obtain the dose-effect relationship for cocaine self-administration in a single 5-6 h daily test session. Rats were pretreated with GBR 12909 (3.0-30.0 mg/kg), WIN 35,428 (0.1-1.0 mg/kg) or indatraline (0.03-1.00 mg/kg) 30 min prior to the test session. RESULTS: GBR 12909 and WIN 35,428 decreased responding maintained by intermediate and high doses of cocaine but indatraline failed to alter the cocaine dose-effect curve. Other groups of rats demonstrated that pretreatment with all three drugs reinstated extinguished cocaine-taking behavior, although indatraline was less efficacious than either GBR 12909 or WIN 35,428. Cocaine-produced drug seeking was enhanced by pretreatment with the highest doses of GBR 12909 and WIN 35,428 but was unaffected by pretreatment with indatraline. A low dose of GBR 12909 that decreased cocaine self-administration failed to produce drug seeking but equal doses of WIN 35,428 were required to decrease cocaine self-administration and to elicit drug seeking. CONCLUSIONS: These data suggest a preferred profile of effects of GBR 12909 as an anti-cocaine pharmacotherapy. It is noted, however, that this drug might be expected to potentiate the ability of cocaine to elicit cocaine seeking following abstinence.

Animals↗

PubMed1998

Effects of beta-funaltrexamine on dose-effect curves for heroin self-administration in rats: comparison with alteration of [3H]DAMGO binding to rat brain sections.

These studies were undertaken to determine the effects of mu-opioid receptor depletion through irreversible alkylation on the dose-effect curve for heroin self-administration. Heroin maintained responding in rats with an inverted U-shaped dose-effect curve and administration of 10 nmol of beta-funaltrexamine i.c.v. (beta-FNA) significantly increased the ED50 on the ascending limb from 1.9 to 5.3 micrograms/infusion, and from 24.3 to 211.8 micrograms/infusion on the descending limb. Administration of saline i.c.v. produced no effect on heroin self-administration. Administration of 40 nmol of beta-FNA increased the ED50S from 5.1 to 33.9 and from 14.4 to 502.8 micrograms/infusion on the ascending and descending portions of heroin's dose-effect curve, respectively. beta-FNA (40 nmol, i.c.v.) had no effect on cocaine self-administration. [3H]DAMGO binding density was decreased in the caudate and nucleus accumbens by 29 or 54% 24 h after administration of 10 or 40 nmol of beta-FNA i.c.v., respectively. The effects of beta-FNA on heroin self-administration were completely overcome by increasing the dose of heroin however, as the shape and slope of the self-administration dose-effect curve was not different when higher doses of heroin were made available for self-administration compared to control data or saline administration. Therefore, there appear to be spare mu-opioid receptors for heroin for the production of its reinforcing effects in rats. Furthermore, the self-administration dose-effect curves returned to control values prior to the return of [3H]DAMGO binding, further suggesting that the full complement of mu-opioid receptors is not necessary for heroin to produce its reinforcing effects. These findings support the existence of spare mu-opioid receptors for heroin in maintaining self-administration in rats.

Analgesics, Opioid↗

PubMed1995

Dopamine release during cocaine self-administration in rats: effect of SCH23390.

This experiment tested the hypotheses that: (1) self-administration of cocaine would produce an increase in dopamine (DA) oxidation current in the nucleus accumbens (n. acc.); and (2) a faster rate of cocaine intake in the presence of a D1 receptor antagonist would produce a greater increase in DA levels. Rats trained to self-administer cocaine under a fixed-ratio 2 schedule were implanted with stearate-modified graphite paste electrodes bilaterally in the n. acc. The effect of pretreatment with the D1 receptor antagonist, SCH23390, on the DA oxidation current associated with self-administration of cocaine (1 mg/inj.) or saline was investigated using chronoamperometry. Pretreatment with SCH23390 produced a 2-fold increase in the amount of cocaine intake. This in turn resulted in a 2-fold increase in the DA oxidation current recorded in the n. acc. Pretreatment with SCH23390 did not, however, produce any significant change in either the number of saline injections received or the DA oxidation current recorded during saline self-administration. These findings show that cocaine increases DA oxidation currents in the n. acc., and that both the rate of cocaine self-administration and the magnitude of these currents increase even further following SCH23390. The results also imply that the baseline rate of cocaine self-administration does not result in the occupation of all possible DA transporter sites.

Animals↗

PubMed2006

Olanzapine-induced suppression of cocaine self-administration in rhesus monkeys.

The neuropharmacological profile of the atypical antipsychotic, olanzapine, is consistent with a potentially useful medication for cocaine abuse. The present study utilized an i.v. drug self-administration paradigm in nonhuman primates to obtain definitive evidence regarding the effectiveness of olanzapine to modulate the reinforcing effects of cocaine. The effects of olanzapine were compared directly to those of the neuroleptic, haloperidol. Rhesus monkeys (n=7) were trained to self-administer cocaine (0.03-0.3 mg/kg/injection) under a second-order, fixed-interval 600-s schedule with fixed ratio 20 components. Experimental sessions comprised five consecutive fixed intervals, each followed by a 1-min timeout. In drug-interaction experiments, a single dose of olanzapine (0.03-0.3 mg/kg) or haloperidol (0.01-0.03 mg/kg) was administered i.v. 15 min presession for at least three consecutive sessions. In drug-substitution experiments, different doses of olanzapine (0.01-0.1 mg/kg/injection) were substituted for cocaine until responding stabilized. Olanzapine caused dose-related decreases in cocaine self-administration at pretreatment doses that had no overt behavioral effects indicative of sedation. A dose of 0.1 mg/kg eliminated cocaine self-administration in all subjects. In contrast, doses of haloperidol that suppressed cocaine self-administration induced marked sedation and catalepsy. Olanzapine failed to maintain self-administration behavior above saline extinction levels over a range of unit doses. In vivo microdialysis experiments in a second group of awake rhesus monkeys (n=3) confirmed previous reports in rodents that olanzapine effectively increases extracellular dopamine in ventral striatum. The dose of olanzapine that markedly suppressed cocaine self-administration behavior increased dopamine to approximately 190% of control values. Lastly, pretreatment with fluoxetine had no systematic effect on olanzapine-induced increases in striatal dopamine. The results indicate that olanzapine can effectively suppress cocaine self-administration behavior in nonhuman primates at doses that enhance dopamine release but do not maintain drug self-administration.

Animals↗

PubMed2000

Nicotine self-administration in rats: estrous cycle effects, sex differences and nicotinic receptor binding.

RATIONALE: Research on smoking behavior and responsiveness to nicotine suggests that nicotine's effects may depend on the sex of the organism. OBJECTIVE: The present study addressed four questions: 1) Will female rats self-administer nicotine? 2) Does self-administration by females vary as a function of estrous cycle? 3) Does self-administration by females differ from that of males? 4) Does self-administration of nicotine result in up-regulation of nicotinic receptor binding and are these changes similar in males and females? METHODS: Male and female Sprague-Dawley rats were allowed to self-administer nicotine at one of four doses (0.02-0.09 mg/kg, free base) on both fixed and progressive ratio schedules of reinforcement. RESULTS: Females acquired nicotine self-administration across the entire range of doses. Acquisition of self-administration at the lowest dose was faster in females than males. However, few sex differences were found in the number of active responses, number of infusions, or total intake of nicotine during stable fixed ratio self-administration. In contrast, females reached higher break points on a progressive ratio. For both schedules, females had shorter latencies to earn their first infusion of each session and demonstrated higher rates of both inactive and timeout responding. There was no effect of estrous cycle on self-administration during either fixed or progressive ratio sessions. Self-administered nicotine resulted in average arterial plasma nicotine levels between 53 and 193 ng/ml and left hemi-brain levels between 174 and 655 ng/g, depending on dose. Nicotine self-administration produced similar up-regulation of nicotinic receptor binding sites in males and females, as reflected by increased right hemi-brain binding of [3H]-epibatidine, when compared to the brains of untreated control rats. CONCLUSIONS: These results suggest that while males and females may regulate their intake of nicotine similarly under limited access conditions, the motivation to obtain nicotine is higher in females.

Animals↗

PubMed2001

Effect of the kappa-opioid receptor agonist, U69593, on reinstatement of extinguished amphetamine self-administration behavior.

Previous research has indicated that pretreatment with the kappa-opioid receptor agonist, U69593, decreased the ability of experimenter-administered cocaine to reinstate extinguished cocaine self-administration behavior. This effect was specific to cocaine-produced drug seeking since U69593 failed to attenuate the ability of experimenter-administered amphetamine to reinstate extinguished cocaine self-administration behavior. One possibility is that U69593 selectively attenuates the behavioral effects of the drug that was originally self-administered. In order to test this hypothesis, the present study examined the effect of U69593 (0.0 or 0.32 mg/kg) on the reinstatement of extinguished amphetamine self-administration behavior produced by experimenter-administered injections of cocaine and amphetamine. Following extinction of amphetamine self-administration (0.04 mg/kg/infusion) the ability of cocaine (0.0, 5.0, 10.0 or 20.0 mg/kg) or amphetamine (0.0, 0.3, 1.0 or 3.0 mg/kg) to reinstate extinguished self-administration behavior was measured. Both drugs reinstated extinguished responding and the reinstatement was attenuated by pretreatment with U69593. The data indicate that the ability of U69593 to decrease drug seeking is not restricted to subjects experienced with cocaine self-administration. Self-administration history does, however, determine the effect of U69593 on amphetamine-produced drug seeking.

Amphetamine↗

PubMed1997

Nicotine self-administration in rats: strain and nicotine pre-exposure effects on acquisition.

Nicotine has been shown to maintain intravenous self-administration behaviour in humans and laboratory animals. However, factors critical in the initiation of nicotine self administration are not well defined. In particular genetic differences and effects of pre-exposure to nicotine have not been examined. Male Sprague-Dawley or Long-Evans rats were surgically prepared with indwelling jugular catheters and 3 days later received chronic injections of nicotine (0.4 mg/kg SC) or vehicle (saline, 1 ml/kg) for 7 days in their home cage. The next day, 2-h daily test sessions were initiated, during which rats were given the opportunity to nose-poke for nicotine infusions (0.015, 0.03 or 0.06 mg/kg per infusion) under a one-response fixed-ratio (FR-1) schedule of reinforcement with a 20-s time out after each infusion. One hole was defined as active while pokes in the other hole were recorded but had no scheduled consequence. The response requirement was increased progressively to five (FR-5) over successive sessions. Both saline- and nicotine-pretreated Sprague-Dawley rats showed a preference for the active hole, while only the saline-pretreated Long-Evans rats acquired the self-administration as defined by significant differences between responding in the active versus the inactive holes. The Fisher (F344) and Lewis inbred strains also failed to acquire self-administration of nicotine under these conditions. With Sprague-Dawley and Long-Evans rats that acquired the self-administration, and showed stable levels of maintained responding for nicotine, substituting saline for the nicotine or pretreating with mecamylamine (2.0 mg/kg SC) extinguished the behaviour. When dose per infusion was varied, an inverted U-shaped dose-response curve was obtained. These results support previous reports that nicotine can serve as a reinforcer in rodents and demonstrate that environmental factors such as prior nicotine exposure or genetic factors such as rat strain can affect acquisition of nicotine self-administration.

Animals↗