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1.
OBJECTIVE: The initial drink of alcohol is often conceptualized as "priming" the individual for the following drinking bout. For the alcoholic, this priming effect has been considered a key for the loss of control that then occurs. Although there have been a few animal studies examining the effects of an investigator-administered ethanol preload on subsequent ethanol self-administration, the effects of a small self-administered oral preload on subsequent consumption have not been examined. METHOD: Adult, male rats, initiated to self-administer ethanol using the sucrose-substitution procedure, were given brief access periods to drink ethanol or water, 5 minutes prior to a second opportunity to press a lever for an additional 20-minute access to a 10% ethanol solution. A second group of rats were trained to press a lever to gain access to a 3% sucrose solution, and the effects of sucrose or water preloads were examined and compared with results in the ethanol group. Results: In the ethanol group, both the ethanol and water preload intakes increased as preload access time increased and were not different from each other. However, ethanol preloads at the longer access times (60 seconds and 120 seconds) decreased subsequent ethanol consumption and at the highest time also affected ethanol-seeking behavior. Equal volumes of water intake at these longer access times had no effects on subsequent ethanol consumption. In the sucrose group, sucrose preload intakes increased as access time increased, but water preload intakes did not. Neither sucrose nor water preloads had any effect on subsequent sucrose consumption. CONCLUSIONS: The data failed to find any priming effect of ethanol preloads in terms of increased subsequent ethanol consumption. It appears that a major factor in the regulation of ethanol intake for the rat in this training procedure is the postingestional effects of ethanol, because taste stimuli did not appear to be important. However, it appears that these ethanol postingestive stimuli are not identical to those involved in the regulation of sucrose consumption.  相似文献   

2.
The purpose of this experiment was to examine the effects of a nondrug alternative reinforcer and feeding conditions on the acquisition of cocaine self-administration. Rats were autoshaped to press a lever that resulted in a 0.2 mg/kg IV cocaine infusion. Responses on the lever were monitored during six consecutive autoshaping sessions that occurred each day. A retractable lever was inserted into the operant chamber on a random time 60 s schedule 10 times per session for six sessions that began each hour. Each day the six autoshaping sessions were followed by a 6-h cocaine self-administration session. During self-administration the lever remained extended, and each response on the lever resulted in a cocaine infusion (0.2 mg/kg). The criterion for acquisition of cocaine-reinforced behavior was met when there were 5 consecutive days during which the mean number of infusions during the 6-h self-administration session was at least 100. This procedure was repeated daily until the criterion was met or 30 days elapsed. The rats were also trained to respond on lick-operated automatic drinking devices that delivered 0.05 ml water or a glucose and saccharin solution (G+S) contingent upon each lick response. Five groups of 12–14 rats were compared. The first four groups constituted a 2 × 2 factorial design whereby either G+S or water was available in the home cage for 3 weeks before autoshaping began and G+S or water was available in the operant chamber during autoshaping. These groups were limited to 20 g food per day and all had free access to water. A fifth group had only water available in the home cage and operant chamber, and they had unlimited access to food but no G+S. The results indicated that access to the G+S solution in the operant chamber substantially delayed autoshaping, and a large percentage of these rats did not meet the autoshaping criterion within 30 days. The data from groups that had G+S in the home cage were very similar to those that had only water in the home cage; thus, a history of access to G+S did not interfere with acquisition of cocaine self-administration. Autoshaping in the group that had free access to food was highly variable, but a high positive correlation was found between the amount of food consumed and the number of days taken to meet the acquisition criterion. When the rats from the group that consumed over 20 g were compared to the rats in another group that were limited to 20 g and had no G+S, it was found that the increased food intake markedly decreased the rate of acquisition of cocaine self-administration. These findings indicate that acquisition of cocaine-reinforced behavior is delayed or prevented in environments enriched with nondrug alternative reinforcers such as food and a preferred liquid.  相似文献   

3.
Sixteen male albino rats were divided into two groups of eight animals and maintained at either their free-feeding or at 80% of their free-feeding weight. For four animals, access to 8% ethanol was unrestricted, for the remaining four, access was restricted to eight 20-min access periods per day. Mean amounts of ethanol consumed per bout were greater during restricted access than during unrestricted access for food-deprived animals but not for free-feeding animals. Total daily ethanol consumption was greatest when animals were food deprived and access to ethanol unrestricted. Total fluid consumption and the within session distribution of water and ethanol responding were affected by feeding condition. For food-deprived animals, the amount of water consumed per session remained relatively constant. The increase in ethanol consumption over sessions resulted in an increase in total fluid consumption. For the free-feeding animals, increases in ethanol consumption resulted in decreases in water consumption so that total fluid consumption remained constant. In addition, food-deprived animals consumed all their daily water intake at the beginning of each session when food was present. Free-feeding animals consumed water throughout the session.  相似文献   

4.
The goal of the present study was to develop and validate an animal model of unlimited access to intravenous heroin self-administration combined with responding for food and water to characterize the transition to drug dependence. Male Wistar rats were allowed to lever press for heroin (60 microg/kg/0.1 ml infusion/s; fixed ratio 1; 20-s time out) and nosepoke for food and water in consecutive, daily 23-h sessions. Daily heroin intake increased over days, reaching significance by Day 14. Drug-taking increased across the circadian cycle, reflected as increases in both the nocturnal peak and diurnal nadir of heroin intake. Changes in the circadian pattern of food intake and meal patterning preceded and paralleled the changes in heroin intake. By Day 7, the circadian amplitude of feeding was blunted. Nocturnal intake decreased because rats consumed smaller and briefer meals. Diurnal intake increased due to increased meal frequency, whereas total daily food intake decreased. To control for time or experience in the self-administration boxes as a possible confound, rats with saline (no drug) tethers were tested and did not display significant changes in food intake pattern. Body weight gain slowed slightly in heroin rats relative to saline controls. Separate groups of rats revealed that significant physical dependence as measured by physical signs of opiate withdrawal following a naloxone injection (1.0 mg/kg, subcutaneous (s.c.)) was reached by Day 14. Significant increases in heroin intake could be produced using low doses of naloxone (0.003-0.03 mg/kg, s.c.) on days 28-31 of heroin access. After 6 weeks of heroin self-administration, rats injected with buprenorphine (0, 0.01, 0.04, and 0.2 mg/kg, s.c.) showed a dose-dependent reduction in heroin intake. Changes in the pattern of drug and food intake in the present unlimited heroin access model may serve as independent motivational markers for the transition to a drug-dependent state.  相似文献   

5.
A novel procedure for initiation of voluntary ethanol consumption in the rat was evaluated in terms of ease of initiation, consistency, and resulting brain ethanol levels. The "jello shot" consists of 10% ethanol in gelatin along with a caloric source (Polycose). Initiation of "jello shot" consumption in Sprague-Dawley rats required no food or water restriction and resulted in initial daily (8.4+/-0.6 g/kg body weight) and eventual hourly (1.1+/-0.1 g/kg body weight) intake of ethanol comparable to other procedures using either alcohol-preferring or non-genetically selected rats. Rat intake of ethanol via "jello shots" recovered quickly from environmental alterations and surgical implantation of a guide cannula. During 1-h free access sessions, consumption of the "jello shot" occurred during the initial 10 min and resulted in a dose-related increase in ethanol levels in nucleus accumbens measured using microdialysis. These brain ethanol levels were comparable to those achieved using other self-administration methods. However, when 0.5 g/kg ethanol was gavaged either in "jello shot" or saline, there was about a 20% decrease in brain ethanol concentrations after gavage of the "jello shot" compared to saline. Even so, lack of a need for initial food or water deprivation and the rapidity with which stable self-administration can be achieved both suggest utility of the "jello shot" as a completely voluntary ethanol procedure.  相似文献   

6.
During daily two-hr sessions, guinea pigs licked a drinking tube filled with either 0 (tap water), 2, 4 or 8% (v/v) ethanol solution under three feeding regimens. Consumption of each solution was highest when sufficient food to maintain subjects at 90% of free-feeding weight was provided during sessions, lower when the same food ration was provided after sessions, and lowest when ad lib access to food was provided within and between sessions. However, this decrease in consumption across feeding regimens was inversely related to ethanol concentration. Under all feeding regimens, volume of solution consumed decreased with increasing ethanol concentration while milligrams ethanol consumed increased with ethanol concentration. These results are similar in some respects to previous findings with rats and monkeys, suggesting that further studies of oral ethanol self-administration by guinea pigs may be merited.  相似文献   

7.
RATIONALE: Dopamine D2 receptors are postulated to play an important role in modulating the reinforcing effects of abused drugs including ethanol. OBJECTIVES: This experiment examined operant ethanol self-administration in dopamine D2 receptor knockout (KO) mice and wild-type (WT) mice using a continuous access procedure. METHODS: Adult male KO and WT mice were trained in 30-min sessions to perform a lever press response for access to 10% v/v ethanol. After training, the mice were placed in test chambers on a continuous (23 h/day) basis with access to food (one lever press, i.e., FR1), 10% v/v ethanol (four lever presses, i.e., FR4), and water from a sipper tube (phase 1). After 30 consecutive sessions, response patterns were determined for 0, 5, 10, 20 and 30% v/v ethanol (phase 2). Saccharin (0.2% w/v) was subsequently added to the ethanol mixture and responding was examined for 0, 5, 10 and 20% ethanol (phase 3). RESULTS: During phase 1, WT mice displayed higher ethanol-lever responding compared to KO mice. Food lever responding and water intake was the same in both genotypes. During phase 2, WT mice displayed concentration-dependent ethanol lever responding, whereas KO mice responded at low rates regardless of ethanol concentration. WT mice also responded more for food compared to KO mice. Each genotype showed similar water intakes except at the 20% ethanol concentration, where WT mice had lower intakes. During phase 3, WT mice continued to show higher responding for all concentrations including saccharin alone. WT mice also continued to respond more for food compared to KO mice, but drank less water. In each phase, WT mice displayed episodic (bout) responding on the ethanol lever. KO mice did not respond for ethanol in bouts. CONCLUSIONS: Reduced responding in the KO mice for several reinforcers including ethanol indicates a more general role for dopamine D2 receptors in motivated responding rather than a specific role in ethanol reinforcement.  相似文献   

8.
Rats housed in three-lever, operant-conditioning chambers were trained under a concurrent, chained fixed-ratio 1, fixed-ratio 9 schedule (conc chain FR1 FR9) of food and water deliveries. After stable patterns of food and water intake were observed, the rats were prepared with intravenous catheters and a drug self-administration option was added to the schedule. Cocaine infusions (0.33 mg/infusion) were available for only 6 h (09.00 h-15.00 h), while access to food and water was available for 24 h. Addition of the cocaine option produced a minimal decrease in food and water intake and a considerable disruption ruption of food and water intake patterns. Changes in the cocaine dose (0.08-0.84 mg/infusion) did not alter responding on the levers resulting in either food or water deliveries. Cocaine self-administration, however, showed an inverted "U" shaped function as the dose of cocaine was increased. Drug extinction probes resulted in a significant increase in responding on the levers resulting in food and water deliveries and substantial decreases on the lever previously resulting in cocaine infusions. Twenty-four hour food extinction probes decreased responding on the levers resulting in food and water deliveries and produced a modest decrease in the self-administration of cocaine.  相似文献   

9.
Reexposure to alcohol may induce subjective craving and relapse to drug self-administration in ex-alcoholics. In this study, we proposed a rat model of "first-drink"-induced drug-seeking relapse. Responding was established in Long Evans rats under a fixed-ratio [FR5:S(1)] schedule for oral ethanol. Substitution of water for ethanol solution resulted in extinction of the self-administration. When responding for 8% ethanol and ethanol intake were stable for at least three consecutive 30min sessions, ethanol delivery was discontinued and only three water dipper cup presentations were available upon responding (3[FR5:water]). When the number of active lever presses decreased to a low stable level, responding was considered extinguished. In Experiment 1, subjects under "extinction" were challenged with three 8% ethanol dipper cup presentations. The re-exposure to ethanol was able to significantly reinstate responding in all subjects. Latency to complete the ethanol presentation significantly decreased compared to the value observed during the previous "extinction" session. In Experiment 2, other subjects were tested for extinction and then reexposed to 4, 8 or 16% ethanol. All three concentrations significantly increased active lever presses, but with different patterns of responding. The resumption of responding was linearly correlated to the ethanol concentration but no significant dose-effect relationship was found. In Experiment 3, reexposure to 8% ethanol in nondeprived rats induced a resumption of responding not significantly different from the effect observed in a restricted diet condition. These results demonstrate that ethanol reexposure is able to reinstate ethanol-seeking behaviour in rats with a past history of ethanol self-administration, and that this effect does not depend on a food motivation drive related to the calorific value of ethanol.  相似文献   

10.
Intake of sweet-alcoholic drinks during adolescence is believed to favor alcohol abuse and dependence in adulthood. This study examined the influence of early exposure to ethanol with or without sucrose on the consumption of sweet or alcoholic solutions in adulthood. Adolescent rats (from post-natal day 30-46) were given continuous free access to tap water and either 5% sucrose, 5% ethanol or mixed 5% sucrose-5% ethanol. The control group was given access to water only. Upon reaching adulthood (post-natal day 60), rats were tested for saccharin (sweet), quinine (bitter) and ethanol consumption using a two-bottle free-choice paradigm. The results indicated that pre-exposure to ethanol did not alter the intake of sweet or ethanol solutions in adulthood. However, rats exposed to sucrose during adolescence showed a decreased consumption of both sweet and ethanol solutions. Because alcohol has a sweet taste component, an additional group of rats, pre-exposed to either 5% sucrose or water during adolescence, was tested for intravenous ethanol self-administration (preventing oral sensory stimulation) and in a new model of simultaneous access to oral saccharin and intravenous ethanol that results in higher total ethanol intake. Relative to controls, sucrose-exposed rats showed reduced operant self-administration of saccharin, yet no differences were found for intravenous ethanol self-administration. Altogether, these findings indicate that sucrose exposure during adolescence persistently affected the perception of sweet taste reward and thereby alcohol’s acceptance in adulthood.  相似文献   

11.
We explored the effects of short, intermediate, and continuous social stress on daily ethanol and water intake in rats. The study was designed to: (1) detect increases in intake during hours when animals were not stressed; and (2) detect shifts in preference from solutions with high to low alcohol content. Male Long-Evans rats acquired ethanol self-administration using a sucrose-fading procedure, which was followed by continuous access to 10% and 3% ethanol solutions and water. After intake stabilized, rats were exposed to three periods of five consecutive days of social stress, with 8-10 days without stress in between. Short social stress consisted of being attacked and defeated by an aggressive opponent, followed by 30 min exposure to threats by the aggressive male while in a protective cage. Intermediate and continuous social stress consisted of a 6 h or 24 h 'threat of attack' exposure, respectively. All stress exposures reduced daily intake of 10% ethanol, did not cause changes in intake of 3% ethanol, and caused increases in water intake. No compensatory ethanol consumption was observed on stress days or after stress exposure was discontinued. These results are at variance with the hypothesis for increased alcohol consumption during or following social stress episodes.  相似文献   

12.
 The effects of dietary caffeine and the amount and palatability of food on the acquisition of cocaine (0.2 mg/kg) self-administration were examined. Using an autoshaping procedure, seven groups of 13 rats each were trained to press a lever resulting in a cocaine (0.2 mg/kg infusion under a fixed-ratio 1 (FR 1) schedule. One group had ad libitum access to caffeine- (0.2% w/w) admixed food. Three groups had access to 10 g, 20 g or ad lib food each day. Another three groups had the same three amounts of ground food with powdered saccharin (0.2% w/w) added. During daily 6-h autoshaping sessions, ten infusions were delivered each hour under a random-time 90-s schedule after a brief (15 s) extension of a retractable lever. These were followed by 6-h self-administration sessions, when the lever remained extended and cocaine infusions were available under an FR 1 schedule. The acquisition criterion was self-administration of a mean of 100 infusions over 5 days. Cocaine self-administration was accelerated in the caffeine group compared to the regular chow group. However, by 30 days nearly the same percentage of rats in the caffeine and regular food groups met the acquisition criterion. In the other six groups, as the amount of food increased, the rate of acquisition and percentage of rats per group meeting the acquisition criterion decreased. In the ad lib group, acquisition was further reduced when saccharin was added to food. In summary, dietary caffeine accelerated acquisition and a greater amount and increased palatability of food independently interfered with acquisition of cocaine self-administration in rats. Received: 9 August 1997 / Final version: 14 November 1997  相似文献   

13.
The effects of three early ethanol home cage consumption procedures on the maintenance of operant lever responding reinforced by ethanol presentation were examined in the rat. Two groups of rats, 25 and 31 days of age, were exposed to 10% (v/v) ethanol as the only fluid in the home cage for 3 or 10 days. A third group, 31 days of age, were exposed to 10% ethanol or tap water for 24 h, with the fluid alternating daily for 18 days. All animals were subsequently trained to lever press using 10% ethanol reinforcement under a decreasing water restriction schedule. All three groups were found to have substantial ethanol consumption levels during the initial exposure in the home cage, ranging from 11.2 to 11.9 g/kg/day. The animals were all successfully trained to lever press in the operant chamber with ethanol as the reinforcer when limited to 15 ml/day of water in the home cage. The average number of reinforcements per day ranged from 29 to 43.5, yielding ethanol intakes from 1.06 to 1.97 g/kg in the 30-minute operant session. However, when 50 ml/day of water was available in the home cage, ethanol reinforcements were substantially reduced, with intakes which ranged from 0.14 to 0.18 g/kg/day. The data suggest that early exposure does not enhance ethanol's reinforcing properties later in the animal's life. These results were discussed in terms the effect of early ethanol exposure on later ethanol consumption and the role of ethanol initiation procedures in oral self-administration.  相似文献   

14.
Rationale Previous research in humans suggests a relationship between drug abuse and impulsivity as shown by selection of a smaller immediate reward over a larger delayed reward. However, it is not clear whether impulsivity precedes drug abuse or drug abuse influences impulsivity.Objective The hypothesis of the present experiment was that rats selected for choosing smaller, immediate over larger, delayed food would acquire IV cocaine self-administration faster than those choosing larger, delayed food rewards.Methods Female rats were screened for locomotor activity and trained on a delay discounting procedure that allowed them access to two response levers and a food pellet dispenser. Under a fixed-ratio (FR) 1 schedule, responding on one lever resulted in immediate delivery of one 45 mg pellet, while responding on the other lever resulted in delivery of three 45 mg pellets after a variable delay that increased after responses on the delay lever and decreased after responses on the immediate lever. For each rat, a mean adjusted delay (MAD) was calculated for each daily session, and stability was defined as MADs varying less than 5 s across 5 days. Based on their average MADs, rats were separated into low impulsive (LoI) and high impulsive (HiI) groups, implanted with an indwelling IV catheter, and trained to lever press for cocaine (0.2 mg/kg) under an FR1 schedule.Results There were no differences in locomotor activity between the LoI and HiI groups; however, a greater percentage of the HiI group acquired cocaine self-administration, and they did so at a significantly faster rate than the LoI rats.Conclusions Performance on the delay discounting model of impulsivity predicted vulnerability to subsequent acquisition of cocaine self-administration.  相似文献   

15.
A major obstacle in the development of new medications for the treatment of alcohol use disorders (AUDs) has been the lack of preclinical, oral ethanol consumption paradigms that elicit high consumption. We have previously shown that rats exposed to 20% ethanol intermittently in a two-bottle choice paradigm will consume two times more ethanol than those given continuous access without the use of water deprivation or sucrose fading (5–6 g/kg every 24 h vs 2–3 g/kg every 24 h, respectively). In this study, we have adapted the model to an operant self-administration paradigm. Long-Evans rats were given access to 20% ethanol in overnight sessions on one of two schedules: (1) intermittent (Monday, Wednesday, and Friday) or (2) daily (Monday through Friday). With the progression of the overnight sessions, both groups showed a steady escalation in drinking (3–6 g/kg every 14 h) without the use of a sucrose-fading procedure. Following the acquisition phase, the 20% ethanol groups consumed significantly more ethanol than did animals trained to consume 10% ethanol with a sucrose fade (1.5 vs 0.7 g/kg every 30 min) and reached significantly higher blood ethanol concentrations. In addition, training history (20% ethanol vs 10% ethanol with sucrose fade) had a significant effect on the subsequent self-administration of higher concentrations of ethanol. Administration of the pharmacological stressor yohimbine following extinction caused a significant reinstatement of ethanol-seeking behavior. Both 20% ethanol models show promise and are amenable to the study of maintenance, motivation, and reinstatement. Furthermore, training animals to lever press for ethanol without the use of sucrose fading removes a potential confound from self-administration studies.  相似文献   

16.
The role for corticotropin-releasing hormone (CRH) receptors in the maintenance of intravenous cocaine self-administration in rats was investigated using the centrally active, small molecule CRH1 receptor antagonist CP-154,526. In these experiments, adult male Wistar rats were allowed alternating 15-min periods of access to food reinforcement and cocaine self-administration (0.125, 0.25 or 0. 5 mg/kg/infusion) during daily 2-h sessions. A 1-min timeout separated access to the two reinforcers. Pretreatment with CP-154, 526 produced dose-related decreases in cocaine self-administration without affecting food-reinforced responding, suggesting a specific effect of the antagonist on cocaine-maintained behavior. Drug intake was decreased across several doses of cocaine, with the dose-response curve for cocaine self-administration shifted downward and flattened, suggesting that CP-154,526 decreased cocaine reinforcement. Furthermore, responding on the cocaine lever following CP-154,526 pretreatment was significantly suppressed, even during the first 15 min of the session, a time when rats typically sample the cocaine lever during extinction, suggesting that CRH receptors may also be involved in some of the conditioned effects of cocaine as well. These data are discussed in terms of the role for CRH in the neurobehavioral effects of cocaine.  相似文献   

17.
Aim: Brucine (BRU) extracted from the seeds of Strychnos nux-vomica L is glycine receptor antagonist. We hypothesize that BRU may modify alcohol consumption by acting at glycine receptors, and evaluated the pharmacodynamic profiles and adverse effects of BRU in rat models of alcohol abuse. Methods: Alcohol-preferring Fawn-Hooded (FH/Wjd) rats were administered BRU (10, 20 or 30 mg/kg, sc). The effects of BRU on alcohol consumption were examined in ethanol 2-bottle-choice drinking paradigm, ethanol/sucrose operant self-administration paradigm and 5-d ethanol deprivation test. In addition, open field test was used to assess the general locomotor activity of FH/Wjd rats, and conditioned place preference (CPP) was conducted to assess conditioned reinforcing effect. Results: In ethanol 2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days dose-dependently decreased the ethanol intake associated with a compensatory increase of water intake, but unchanged the daily total fluid intake and body weight. In ethanol/sucrose operant self-administration paradigms, BRU (30 mg/kg) administered before each testing session significantly decreased the number of lever presses for ethanol and the ethanol intake, without affecting the number of sucrose (10%) responses, total sucrose intake, and the number of lever presses for water. Acute treatment with BRU (30 mg/kg) completely suppressed the deprivation-induced elevation of ethanol consumption. Treatment with BRU (10, 20, and 30 mg/kg) did not alter locomotion of FH/Wjd rats, nor did it produce place preference or aversion. Conclusion: BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism.  相似文献   

18.
Responding by six rats was maintained under a concurrent chained fixed-ratio 1, fixed-ratio 9 schedule (conc chain FR1 FR9) of food, water, and morphine presentations. The subjects had continuous access to the schedule contingencies on a reversed 12-h light-dark cycle. Local rates and temporal patterns were very similar for responding maintained by the three reinforcers with food and water intake occurring predominantly during the dark cycle, while morphine infusions were evenly distributed. Food and water extinction (24-h duration) decreased the number of ratios completed on both the food and water levers. Moreover, food extinction resulted in a large increase in I.V. morphine self-administration. Morphine extinction increased responding on the morphine lever while almost eliminating responding on the water lever. Changes in the dose of morphine (2.5–40 mg/kg/injection) did not significantly affect food and water intake, but were inversely related to responding on the morphine lever. Saline substitutions resulted in effects similar to those observed during morphine extinction. The schedule used in this study provides a method for examining the specificity of a number of pharmacological and neurochemical manipulations.  相似文献   

19.
Nicotine self-administration in rats   总被引:5,自引:3,他引:2       下载免费PDF全文
Female Wistar rats were allowed to self-administer nicotine solutions through indwelling jugular vein cannulae for 23 h per day for periods from three to five weeks. Two response levers were available to the rats; responding on one lever, designated the active lever, produced an immediate infusion of nicotine solution or saline. A second lever for which responding had no programmed consequences was introduced as a control for the locomotor stimulant action of low doses of nicotine. Baseline lever response rates were determined over a period of one week, in which active lever responding produced an infusion of saline. Rats were then allowed access to varying doses of nicotine or saline for a further two or three weeks. Response rates on the active lever increased significantly in rats with access to nicotine at a dose of 30 micrograms kg-1 per response. However, control lever response rates were also significantly elevated. The role of nicotine-induced locomotor stimulation in the self-administration behaviour was further evaluated in a dose-reduction experiment, in which the dose of nicotine available to rats responding for 30 micrograms kg-1 per response was reduced to 3 micrograms kg-1 per response. This resulted in a significant differential increase in active lever responding relative to control lever responding. The results suggest that nicotine is positively reinforcing in rats which had not previously been deprived of food or water or received prior drug treatment, but also indicate that nicotine induced locomotor stimulation may contribute to the observed increases in lever response rates when rats self-administer nicotine.  相似文献   

20.
The purpose of this experiment was to evaluate the effects of morphine self-administration on wheel running and wheel running-reinforced lever pressing in rats. The home cage was equipped with a bottle that contained either water, a saccharin-flavored 0.5-mg/ml morphine solution, or saccharin (0.25%). The bottle was available for either 1 or 3 h. The bottle was then removed, and 20-22 h after removal, the rats were moved to an operant chamber in which lever presses earned 15 s access to a running wheel (according to a variable interval (VI) 40-s schedule). The morphine condition was in effect for 69 days, and consumption gradually increased to a level of 67 mg/kg/day. During the morphine condition, wheel running and lever pressing decreased. Following the removal of morphine, (so that the home-cage bottles provided a 0.25% saccharin solution), the two instrumental behaviors increased to the pre-morphine (water) levels. However, the increases were not immediate, and in the first post-morphine session, lever pressing and wheel turning remained at the depressed morphine level. The post-morphine increase in lever pressing was substantially larger than the increase in wheel running. The results support the hypothesis that chronic opiate consumption reduces the frequency of some nondrug-related behaviors, and that this, in turn, increases preference for the opiate.  相似文献   

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