Biomedical subjects

M E Carroll

Publications and source records attributed to M E Carroll.

At least 19 recordsLinked to original sources

PubMed2001

Effects of ketoconazole on the acquisition of intravenous cocaine self-administration under different feeding conditions in rats.

RATIONALE: Ketoconazole, an inhibitor of corticosterone synthesis, has been reported to decrease the self-administration of low doses of cocaine and prevent stress-induced reinstatement of cocaine-reinforced behavior in rats. OBJECTIVES: The effects of ketoconazole were extended to the acquisition of i.v. cocaine self-administration during food restriction, a form of stress. Food restriction accelerates the acquisition of cocaine self-administration, and the purpose of this experiment was to determine whether ketoconazole would block the food-restriction effect. As control conditions, the effects of ketoconazole on the acquisition of cocaine self-administration in food-satiated rats and acquisition of food-reinforced responding were also evaluated. METHODS: Six groups of rats (groups 1-6) were trained to self-administer i.v. cocaine (0.2 mg/kg; groups 1-4) or food pellets (45 mg; groups 5 and 6) under a fixed-ratio 1 (FR 1) schedule. Food availability was restricted to 20 g per day in groups 1, 2, 5, and 6, while groups 3 and 4 were fed ad libitum. Daily sessions included a 6-h autoshaping component followed by a 6-h self-administration component. During autoshaping, 10 infusions or food pellets were delivered each h under a random interval 15-s schedule after extension and retraction of a lever. During self-administration, the lever remained extended and infusions or food pellets were available under an FR 1 schedule. The criterion for acquisition was a 5-day period during which a mean of 100 cocaine infusions or 150 food pellets was obtained during the self-administration component. Rats were given 30 days to reach this criterion. They were pretreated with ketoconazole (25 mg/kg, i.p.; groups 1, 3, and 5) or vehicle (i.p.; groups 2, 4, and 6) 30 min prior to the autoshaping and self-administration components. RESULTS: Pretreatment with ketoconazole decreased both the rate of acquisition of cocaine self-administration and the percentage of rats meeting the acquisition criterion but only under food-restricted conditions. Ketoconazole had no effect on the acquisition of food-reinforced responding. CONCLUSIONS: These results extended previous findings of the suppressant effects of ketoconazole on cocaine-reinforced responding in rats to the acquisition of cocaine self-administration using food restriction as a stressor.

Animals↗

PubMed2001

Role of estrogen in the acquisition of intravenously self-administered cocaine in female rats.

Previous work from this laboratory has revealed that female rats acquired cocaine self-administration at a faster rate than male rats and that a greater percentage of females acquired self-administration [Psychopharmacology 144 (1999) 77.]. It has been suggested that sex differences in stimulant self-administration may be related to ovarian hormones, particularly estrogen. To investigate this possibility, we compared four groups (n = 10) of female rats: ovariectomized (OVX) treated with either estradiol benzoate (EB) or vehicle (VEH), and sham-operated intact (SH) females treated with either the antiestrogen tamoxifen (TAM) or VEH. An autoshaping procedure was used to train rats to lever press for intravenous infusions of cocaine (0.2 mg/kg). The criterion for cocaine acquisition was a mean of 100 self-administered infusions over five consecutive 6-h sessions. Results revealed that 70% of the OVX + EB group and 80% of the SH + VEH group acquired self-administration, while only 30% of the OVX + VEH group and 50% of the SH + TAM group met the acquisition criterion. Rats that had estrogen chemically or surgically blocked exhibited significantly less responding for cocaine over the acquisition testing period, and fewer of these rats met the acquisition criterion compared to intact rats and to OVX rats with estrogen (EB) replacement. The percentages for females with estrogen (70% and 80%) vs. those without (OVX, 30%) were similar to those reported for intact females (70%) and males (30%) in the previous study [Psychopharmacology (2000)]. Taken together, these results suggest that estrogen is a key factor influencing drug-seeking behavior in female rats, and it may underlie sex differences in drug-reinforced responding.

Animals↗

PubMed2001

Regulation of drug intake.

Regulation of drug intake refers to the maintenance of relatively constant levels of drug over a specified time period. An understanding of regulation of drug intake may be critical in determining how drugs function as reinforcers and how their reinforcing effects may be modified. However, little is known about regulation of drug intake, and the mechanisms underlying it are poorly understood. Three mechanisms that have proposed to account for findings of regulation of drug intake were discussed to determine their relevance for drug-reinforced responding. These mechanisms include aversive effects, direct effects, and satiation. Although a greater role for satiation was supported in this review, drugs may vary on the degree to which they can produce satiation and whether satiation acts in concert with either the aversive effects or the direct effects of drugs is unclear.

Humans↗

PubMed2001

Ketoconazole suppresses food restriction-induced increases in heroin self-administration in rats: sex differences.

The effects of ketoconazole, an inhibitor of corticosterone synthesis, were examined during food satiation and food restriction in male and female rats to determine whether increases in heroin self-administration prompted by food restriction were due to a stress response. Females self-administered more heroin infusions than males under both feeding conditions. Food restriction increased heroin infusions by an average of 96% for both females and males. Ketoconazole suppressed the increase due to food restriction in females but not in males. Corticosterone reversed the effect of ketoconazole in a group of 8 females, suggesting an interaction between feeding conditions, sex, and the stress response in rats.

Animals↗

PubMed2000

Acquisition of oral phencyclidine self-administration in rhesus monkeys: effect of sex.

RATIONALE: There are increasing reports of sex differences in the etiology of drug abuse in humans. A nonhuman primate model is useful for examining sex as a variable in drug abuse. OBJECTIVES: To determine whether there are sex differences in the acquisition of oral phencyclidine (PCP) self-administration and to compare the effect of altered feeding conditions on drug self-administration in male and female monkeys. METHODS: Acquisition of orally delivered PCP was studied using 7 female and 11 male adult rhesus monkeys. Initially, the monkeys were not food restricted, and they were given access to water under concurrent fixed-ratio (FR) 1 schedules during daily 3-h sessions. Each lip-contact response on a drinking spout resulted in a 0.3 ml liquid delivery. After baseline levels of water intake were obtained for 5 days, water was replaced with PCP (0.125 mg/ml) at both drinking spouts. Body weights were then reduced to 85% of free-feeding weights, and the monkeys were fed 30 min before the session began. The FR value was increased from 1 to 2, 4, and 8, at both drinking spouts. As a final step in the procedure, water and PCP were concurrently available at the two spouts under FR 8 schedules. Acquisition of PCP-reinforced behavior was considered to have occurred if PCP intake was consistently greater than water intake. RESULTS: Lip-contact responses and liquid deliveries were not significantly different between the females and males throughout the acquisition period, but there was a significant increase in responding and decrease in liquid intake as FR increased, and a significant increase in PCP consumption due to food restriction that did not differ in males and females. On a milligram per kilogram basis, female monkeys consumed nearly twice as much PCP as the males; however, this effect was not significant. The females showed significantly higher PCP than water intake while the males consumed approximately equal amounts of PCP and water. Of the seven females, 100% met the acquisition criterion of significantly greater PCP than water intake, while only 36.4% of the males met the criterion. CONCLUSION: These results concur with previous rat studies and indicate that female monkeys are more likely than males to acquire drug-reinforced behavior.

Animals↗

PubMed2000

Effects of sex and the estrous cycle on regulation of intravenously self-administered cocaine in rats.

RATIONALE: Previous research with both humans and animals suggests that there are sex differences in cocaine self-administration; in rodents, ovarian hormones may underlie these differences. OBJECTIVES: A two-lever drug self-administration procedure was used to compare regulation of intravenously self-administered cocaine in male and female rats and among females in different phases of the estrous cycle. METHODS: Eleven female and seven male age-matched Wistar rats were trained to self-administer nine doses of cocaine (0.0-2.4 mg/kg) during daily 5-h sessions. Experimental test chambers were equipped with two levers and associated stimulus lights. A response on the lever with stimuli signaling an increase in cocaine dose increased the infusion duration by 3 s, and a response on the other lever decreased the infusion duration by 3 s. RESULTS: After responding for cocaine stabilized, regulation was disrupted more in females than in males (r2=78.9, r2=92.6, respectively) with the greatest disruption observed in females during the estrus phase (r2=48.5). Mean dose size varied considerably for males and for females in the metestrus/diestrus and proestrus phases; however, estrus females responded almost exclusively on the lever associated with an increase in cocaine dose. CONCLUSIONS: These findings indicate sex differences in the regulation of cocaine self-administration, and they suggest that ovarian hormones may be responsible for the observed sex differences.

Animals↗

PubMed2000

Deconstructing relative reinforcing efficacy and situating the measures of pharmacological reinforcement with behavioral economics: a theoretical proposal.

BACKGROUND: Relative reinforcing efficacy has been assumed to be a homogeneous phenomenon referring to the behavior-strengthening or behavior-maintaining effects of a drug reinforcer. However, a variety of studies suggest that relative reinforcing efficacy may be heterogeneous. OBJECTIVES: The purpose of this theoretical proposal is to examine the difficulties associated with this conception of reinforcing efficacy and to explore whether relative reinforcing efficacy is a homogenous concept or whether it is composed of several functionally related heterogeneous phenomena. In examining this issue, we explore whether behavioral economic theory may address some of the challenges to the current conception of relative reinforcing efficacy and use this theory to suggest how the differing measures of reinforcing efficacy may relate to one another. RESULTS: Results indicate that peak-response rate and breakpoint are related to the economic measure of maximal output and elasticity of demand, respectively. Preference is related to and predicted by the relative location of the demand curves obtained under single schedule conditions. This behavioral economic analysis may provide a theoretical understanding of reinforcement that can reconcile results of studies that both support and fail to support the notion of reinforcing efficacy as a homogenous phenomenon. CONCLUSIONS: If this theoretical proposal is validated by additional studies, then like other natural phenomena found to be heterogeneous, the study of drug reinforcers may require the adoption of several new scientific terms, such as those used in behavioral economics, each of which has analytical precision and refers to homogeneous phenomena.

Animals↗

PubMed2000

Reduction of drug self-administration by an alternative non-drug reinforcer in rhesus monkeys: magnitude and temporal effects.

RATIONALE: Recent studies have shown that non-drug alternative reinforcers reduce drug self-administration. A goal of the present study was to explore factors such as magnitude of the alternative reinforcer and inter-session access to the alternative to identify conditions that lead to optimal reductions in drug intake. OBJECTIVES: To evaluate the effects of increasing the volume/delivery (v/d) of saccharin on oral phencyclidine (PCP) self-administration in rhesus monkeys given continuous access to PCP and saccharin during daily sessions using a behavioral economic analysis. The effects of availability of a saccharin solution during the inter-session period on session PCP consumption in drug-experienced monkeys was also investigated. METHODS: Subjects had access to PCP (0.25 mg/ml) and either water or saccharin (0.03%) from two drinking spouts under concurrent and independent fixed-ratio (FR) schedules during daily 3-h sessions. The FR requirements for both available liquids were simultaneously increased (FR4-64). The v/d of saccharin or water was increased (from 0.3 ml to 1.2 ml), while the v/d of PCP remained constant (0.6 ml). In a second experiment, subjects had access to water or saccharin and water during the inter-session period (17.5 h) under an FR1 schedule. PCP and water were available during daily 3-h sessions under concurrent FR schedules. The FR for both liquids was increased (FR16-128). RESULTS: PCP intake was reduced at all FRs and magnitude conditions when saccharin (versus water) was concurrently available. Varying the v/d of saccharin only had a modest effect on the extent to which PCP intake was decreased at the higher FR values. Inter-session saccharin availability (versus water) reduced session PCP intake and the magnitude of this effect was also greater at the higher FR values. CONCLUSIONS: The magnitude of the saccharin delivery had an effect on PCP consumption at higher FRs, suggesting that economic factors such as high drug cost (FR) and low cost (responses/ml) of the alternative reinforcer (saccharin) interact to produce a maximum suppression of drug intake. Between-session availability of saccharin also effectively reduced drug intake, and it had a greater effect on the maintenance levels of drug self-administration when the unit price of drug was high.

Administration, Oral↗

PubMed2000

Reinstatement of cocaine self-administration in rats: sex differences.

RATIONALE: Results obtained with both humans and animals suggest that rates of relapse, or levels of reinstatement responding, may differ between males and females. However, the results obtained with humans are equivocal, and few studies have compared male and female animals on reinstatement responding. OBJECTIVES: The present experiment was designed to compare male (n=8) and female (n=8) rats on reinstatement of extinguished cocaine-reinforced responding. METHODS: Reinstatement of responding was examined using a priming model in which lever pressing for cocaine (0.2 mg/kg) was extinguished by replacing cocaine infusions (2 h) with saline infusions (5 h). After responding extinguished during hour 3, reinstatement of responding was tested by administering one of several priming injections of cocaine (0.32, 1.0 and 3.2 mg/kg) or an equal volume of saline. RESULTS: Although males and females did not differ in the number of saline infusions self-administered after either saline or 0.32 mg/kg cocaine-priming injections, female rats self-administered significantly more saline infusions than males after 1.0 mg/kg and 3.2 mg/kg cocaine-priming injections. Additionally, the effects of 0.32 mg/kg cocaine-priming injections were significantly different from those of saline-priming injections for female, but not male, rats. There was no significant difference between males and females in total cocaine self-administered during hours 1 and 2. CONCLUSIONS: These findings indicate that female rats are more sensitive than males during the reinstatement phase of drug abuse.

Analysis of Variance↗

PubMed2000

Reductions in ethanol, phencyclidine, and food-maintained behavior by naltrexone pretreatment in monkeys is enhanced by open economic conditions.

RATIONALE: Previous results suggested that naltrexone had opioid-selective effects on behavior reinforced by orally delivered drugs and food. The present study explores the possibility that previous results were due to presentation of the reinforcers in a closed economy (all reinforcers earned by subjects) and that naltrexone's effect may be nonselective under conditions of an open economy (earned reinforcers supplemented by unearned). OBJECTIVES: The purpose of this experiment was to compare the effect of naltrexone on ethanol-, phencyclidine-(PCP), and food-reinforced responding under several open-economy conditions and compare them with those from a previous report using a closed economy. METHODS: Ethanol (8% w/v), PCP (0.25 mg/ml), and food were available under independent, concurrent, progressive-ratio (PR) schedules with water, and side positions were alternated daily. Three naltrexone doses (0.1, 0.3, and 1.0 mg/kg) were administered in a nonsystematic order for 5 days, with the 5-day pretreatment period serving as a control. Four economic conditions were compared: data for the closed economy were taken from a recently completed experiment using the same monkeys. The open-economy condition was varied by allowing free access to 1, 2 or 3 times the amount of drug or food that was earned during session later during a postsession time-out period. RESULTS: In an open economy, naltrexone nonselectively suppressed ethanol, PCP, and food-maintained behavior, in contrast to results in the previous study which used a closed economy, wherein naltrexone did not significantly suppress food- or PCP self-administration. As the economy for PCP, ethanol, and food became more open, the suppressant effects of naltrexone increased and, in many animals, behavioral measures decreased to zero. CONCLUSION: These results indicated that the economy under which drugs and food are self-administered is an important determinant of the effectiveness of naltrexone's ability to suppress drug- and food-reinforced behavior. The results also suggest that testing medications for drug abuse using a food control condition under a closed economy can bias the results toward a conclusion of selectivity of the treatment medication for drug-reinforced behavior.

Animals↗

PubMed2000

Acquisition of drug self-administration: environmental and pharmacological interventions.

The development of drug-reinforced behavior is a transition process characterized by a relatively rapid shift from little or no drug-maintained responding to high, stable levels of responding. Animal studies of drug self-administration focus on how rapidly this process takes place or what percentage of animals acquire drug self-administration. It is essential to have animal models of acquisition because the process is difficult to study with drug-naive humans. Animal studies reveal a wide range of factors that can either accelerate or decrease acquisition of drug self-administration, such as environmental conditions (e.g., feeding conditions, palatable dietary substances, stress), pharmacological variables (e.g., drug dose, drug history, pretreatment drugs), and individual differences (e.g., reactivity level, age, sex, dietary preferences, genetics). This article discusses the methods used to study acquisition of drug-reinforced behavior in laboratory animals and the variables that have been reported to accelerate or prevent the acquisition of drug-reinforced behavior. An understanding of the conditions that can enhance acquisition in animals may help predict vulnerability to drug use in humans and lead to successful methods for prevention of drug abuse.

Animals↗

PubMed2000

Quantification of reinforcing effectiveness: comment on Meisch (2000)

R. A. Meisch (2000) introduces an innovative method for quantifying the reinforcing effectiveness of drugs and other substances. Advantages are that it models the persistence of drug use in humans and its persistence ratios are the same whether responding or consumption is measured. Data indicate that the method is sensitive to factors that affect drug self-administration. The measure's core feature is "the systematic variation of both reinforcer magnitude and schedule size" (Meisch, 2000, p. 347); however, the method may not be widely used with such extensive parametric analysis. Variation of only reinforcer magnitude (or dose/concentration) seems to produce similar results, and this abbreviated analysis is similar to the behavioral economic analysis of demand. When responding is plotted as a function of unit price (responses/milligram), the peak of the curve (where maximum responding occurs) is a measure of persistence. Further work will determine how these and other measures of reinforcing effectiveness agree.

Animals↗

PubMed1999

Naltrexone pretreatment decreases the reinforcing effectiveness of ethanol and saccharin but not PCP or food under concurrent progressive-ratio schedules in rhesus monkeys.

The purpose of this experiment was to determine whether attenuation of ethanol consumption by naltrexone is the result of selective changes in the reinforcing effectiveness of drug and non-drug reinforcers. A range of naltrexone doses (0.1-1.0 mg/kg) was administered for 5 days, and the effects on the reinforcing effects of orally delivered 8% (w/v) ethanol, 0.25 mg/ml phencyclidine (PCP), 0.03% (w/v) saccharin and food were studied in eight rhesus monkeys. Food and liquids were available under independent and concurrent progressive-ratio (PR) schedules (ratio range 8-4096) during daily 3-h sessions. Ethanol-maintained responding was attenuated by 0.3 and 1.0 mg/kg doses of naltrexone, while saccharin-maintained responding was decreased at the 1.0 mg/kg dose. Furthermore, there was a significant linear trend that consumption of available ethanol and saccharin was attenuated dose-dependently by naltrexone. Following 5 days of naltrexone pretreatment, ethanol- and saccharin-maintained responding immediately returned to or exceeded baseline levels. Food- and PCP-maintained responding and intake were not significantly affected by any of the naltrexone doses examined. The decreased break point (BP) values for ethanol and saccharin suggest that their reinforcing effects are mediated through opioid reinforcement mechanisms. The lack of naltrexone attenuation of PCP- and food-maintained responding suggests that these reinforcers: 1) are not sensitive to naltrexone antagonism at the doses examined, 2) are mediated by non-opioid reinforcement mechanisms, and/or 3) have less intrinsic palatability.

Animals↗

PubMed1999

Effects of baclofen on maintenance and reinstatement of intravenous cocaine self-administration in rats.

RATIONALE: Recent studies suggest that the GABA(B) receptor agonist, baclofen, may be a useful pharmacotherapy for cocaine abuse. OBJECTIVES: To investigate further the effects of baclofen on maintenance and reinstatement of cocaine-reinforced behavior in rats. METHODS: Two groups of rats were trained to self-administer IV cocaine (0.2 or 0.4 mg/kg per infusion) during daily 7-h sessions under a fixed-ratio 1 schedule. Rats were pretreated with baclofen (1.25, 2.5 or 5 mg/kg IP) or saline before the session for 5 consecutive days. An additional group of rats was trained to self-administer IV cocaine (0.4 mg/kg per infusion) during the first 2 h of daily 7-h sessions. Cocaine was replaced by saline for the remaining 5 h of the session. Once behavior had stabilized over the 7-h period, priming injections of saline (IV), cocaine (3.2 mg/kg IV) or baclofen (1.25 or 2.5 mg/kg IP) were administered prior to hour 4. Injections of baclofen (1.25 or 2.5 mg/kg IP) or saline were also given before priming injections of cocaine. RESULTS: Pretreatment with the two higher doses of baclofen (2.5 and 5 mg/kg) decreased the number of cocaine infusions in both maintenance groups (0.2 and 0.4 mg/kg) over the 5-day treatment period. Baclofen had a greater suppressant effect on responding maintained by the lower dose of cocaine. Priming injections of baclofen (1.25 and 2.5 mg/kg) or saline did not reinstate responding. However, these same doses of baclofen dose-dependently reduced the reinstatement of responding produced by priming injections of cocaine. CONCLUSIONS: 1) The magnitude of the suppressant effects of baclofen on maintenance of cocaine self-administration depends upon the maintenance dose, 2) baclofen may be useful in preventing reinstatement of cocaine-seeking behavior, and 3) compared to maintenance, reinstatement of responding is more sensitive to the suppressant effects of baclofen.

Animals↗

PubMed1999

Sex differences in the acquisition of intravenously self-administered cocaine and heroin in rats.

RATIONALE: Despite numerous reports that male and female animals differ in behavioral responses to drugs, few studies have investigated sex differences in drug-reinforced behavior. OBJECTIVES: Acquisition of IV cocaine and heroin self-administration was compared in 20 female and 22 male Wistar rats. METHODS: An autoshaping procedure was used to train rats to press a lever that resulted in either a 0.2 mg/kg infusion of cocaine or a 0.015 mg/kg infusion of heroin under a fixed-ratio 1 (FR 1) schedule. Daily sessions consisted of six 1-h autoshaping components followed by a 6-h self-administration component. During each autoshaping component, a retractable lever briefly (15 s) extended into the test chamber on a random interval schedule with a mean of either 90 s (cocaine groups) or 480 s (heroin groups) and either ten (cocaine groups) or five (heroin groups) computer-automated infusions were delivered each hour. During each 6-h self-administration component, the lever remained extended and each response on the lever resulted in an infusion of either cocaine (0.2 mg/kg) or heroin (0.015 mg/kg). The criterion for acquisition of cocaine self-administration was a mean of at least 100 infusions and the criterion for heroin self-administration was a mean of at least 20 infusions during the self-administration component over five consecutive sessions. RESULTS: Female rats acquired both cocaine and heroin self-administration more rapidly than males. Acquisition of cocaine self-administration occurred in a greater percentage of female rats compared to males. Female rats self-administered more cocaine than males after acquisition criteria had been met. CONCLUSIONS: These findings indicate that female rats were more vulnerable than males to the acquisition of cocaine and heroin self-administration under the conditions of the present experiment.

Animals↗

PubMed1999

Concurrent progressive-ratio schedules to compare reinforcing effectiveness of different phencyclidine (PCP) concentrations in rhesus monkeys.

RATIONALE: Progressive ratio (PR) schedules have become well accepted for testing the reinforcing effectiveness of drugs. This study extends the methods to concurrent PR schedules with different concentrations of orally delivered phencyclidine (PCP). OBJECTIVE: The sensitivity of the procedure is tested by presenting different PCP concentrations with independently-operating PR schedules. METHOD: PCP self-administration was investigated in seven rhesus monkeys. Six different PCP concentrations (0.03-1.0 mg/ml) and water were randomly paired (21 pairings). Liquid delivery (24 ml) was contingent upon lip-contact responses on solenoid-operated drinking spouts; whereby, the response requirement or fixed-ratio (FR) increased (from 8 to 16, 32, 64, 128... to 4096) after each successful completion of a previous FR and subsequent liquid delivery. Monkeys self administered PCP during daily 3-h sessions, and each pair of concentrations was held constant until behavior had stabilized for at least 4 days. RESULTS: The higher of the two PCP concentrations always maintained greater responding, PR break point (BP), or the last ratio completed, and liquid deliveries than did the lower concentration. However, the monkeys did not exclusively respond on the drinking spout that yielded the higher drug concentration. When examined across all drug pairings, the percentage of total available deliveries of the higher concentration was significantly greater than those of the lower concentration. The monkeys maximized the amount (mg) consumed for the response output. Responding, BPs and liquid deliveries maintained by 0.12 and 0.25 mg/ml PCP were significantly greater than other PCP concentrations; however, drug intake (mg) increased directly with PCP concentration. CONCLUSION: These results indicate that concurrent PR schedules using oral drug self-administration and a concurrent choice paradigm reliably provide an estimation of relative reinforcing strength, and behavior maintained by these schedules is sensitive to small changes in PCP concentration.

Administration, Oral↗

PubMed1999

Effects of dopamine receptor antagonists (D1 and D2) on the demand for smoked cocaine base in rhesus monkeys.

RATIONALE: Previous studies suggest that dopamine antagonists may reduce the reinforcing effects of cocaine. However, the effects of these antagonists on the demand for smoked cocaine base have not been quantified. OBJECTIVES: To evaluate the effects of selective D1 (SCH 23390) and D2 (raclopride) dopamine receptor antagonists on the demand for smoked cocaine base in rhesus monkeys using a behavioral economic analysis. METHODS: Six rhesus monkeys were trained to self-administer smoked cocaine base (1.0 mg/kg/delivery) under chained fixed-ratio (FR) schedules (FR64, 128, 256, 512, 1024 or 2048 for lever presses and FR5 for inhalations) during daily 4-h sessions. A maximum of ten smoke deliveries were available. After 5 days of stable behavior at each FR, SCH 23390 (0.01 and 0.056 mg/kg) or raclopride (0.03 and 0.056 mg/kg) were injected intramuscularly, before each session, for 3 consecutive days. RESULTS: Pretreatment with both antagonists dose-dependently reduced cocaine intake across most FR values tested; however, the decrease in consumption was greater at the higher unit prices than at the lower unit prices. A statistical estimate of the price (FR) at which maximum responding occurred (Pmax) was decreased during drug pretreatment, indicating weakened reinforcing effectiveness of cocaine. CONCLUSIONS: These data suggest that both antagonists reduce the reinforcing effectiveness of smoked cocaine base, and they have a greater effect on cocaine consumption at higher FR values.

Animals↗

PubMed1999

Regulation of intravenously self-administered nicotine in rats.

Ten male Wistar rats had access to 9 doses of nicotine (0.01-0.10 mg/kg i.v.) during daily 5-hr sessions. Once responding for nicotine stabilized, nicotine infusions were replaced with either cocaine infusions (0.0-2.4 mg/kg) or saline infusions. Saline substitution results indicate that nicotine functioned as a reinforcer. Regulation of nicotine intake was compared with that of cocaine by obtaining the correlation between mean interdose interval and preceding dose size. Results reveal that although this correlation was significant for both nicotine and cocaine self-administration, nicotine self-administration was less precisely regulated than cocaine self-administration. This procedure suggests that there are differences in regulation among self-administered drugs and that it may serve as a useful baseline for studying differences in vulnerability to drug abuse and potential treatment strategies.

Animals↗