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1.
Post-weaning housing conditions influence the behavioural effects of cocaine and d-amphetamine 总被引:4,自引:0,他引:4
Post-weaning social isolation can induce profound and long lasting effects on an animal’s behaviour. The present study investigated
the influence of post-weaning housing conditions on the sensitivity of rats to the behavioural effects of d-amphetamine and cocaine. The locomotor stimulant effects of both drugs were compared following acute and chronic administration.
The influence of post-weaning housing conditions on the effects of d-amphetamine and cocaine on responding for food and for a conditioned reinforcer were also examined. Isolated rats showed
enhanced locomotor activity on exposure to a novel environment. This difference was further exaggerated following administration
of d-amphetamine (0.5 mg/kg) and cocaine (5 mg/kg). Isolated, but not enriched, rats exhibited sensitisation to the locomotor
activating effects of repeated administration of a dose of 0.5 mg/kg d-amphetamine, whilst both groups sensitised equally to a dose of 1.0 mg/kg d-amphetamine. Rearing conditions did not affect sensitisation to cocaine (5, 10 mg/kg). Isolated rats exhibited a higher rate
of responding for a conditioned stimulus and for food on a progressive ratio schedule of reinforcement, both of which were
enhanced to a greater extent in isolates following administration of cocaine (5 mg/kg) and d-amphetamine (0.5 mg/kg). These results suggest that isolation rearing induces an enhancement in sensitivity to both the locomotor
stimulant and reinforcing properties of amphetamine and cocaine.
Received: 12 June 1996 / Final version: 17 October 1996 相似文献
2.
We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study
with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice
between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate
drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37 ± 0.02 mg/kg per day, subordinate rats: 0.57 ± 0.05 mg/kg
per day) and environmental variables (group housing: 0.21 ± 0.02 mg/kg per day, single housing: 0.41 ± 0.03 mg/kg per day).
Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9 ± 0.2 mg/kg per day in week 47), although the experimental conditions
remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the
rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external
conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6 ± 0.6 mg/kg per day; age-matched controls:
0.37 ± 0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1 ± 0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during
withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42 ± 0.04 mg/kg per day).
Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol
and opiates.
Received: 3 April 1998/Final version: 26 August 1998 相似文献
3.
Sharon A. Segal Joseph M. Moerschbaecher Donald M. Thompson 《Pharmacology, biochemistry, and behavior》1981,15(5):807-812
The effects of phencyclidine, d-amphetamine, and pentobarbital on responding maintained under a multiple fixed interval (FI) 3-min fixed-ratio (FR) 30 schedule of food presentation were studied in rats. Phencyclidine (0.32–7.5 mg/kg) had a biphasic effect on overall response rate in both components; response rate increased and then decreased as the dose was increased. The FR was slightly more sensitive to the rate-decreasing effects of phencyclidine than the FI. The effects of d-amphetamine (0.1–7.5 mg/kg) on overall rate were qualitatively similar to those of phencyclidine. The FI tended to be slightly more sensitive than the FR to the rate-increasing effects of d-amphetamine. Pentobarbital (1–18 mg/kg) produced little or no rate-increasing effects in the FR at low doses and decreased FR response rate at higher doses. In the FI, pentobarbital produced small increases in overall rate at intermediate doses while decreasing response rate at higher doses. The FR tended to be more sensitive than the FI to the rate-decreasing effects of pentobarbital. Unlike d-amphetamine and pentobarbital, phencyclidine produced smaller rate-increasing effects when the dose-effect curves were redetermined. Within the FI, the effects of phencyclidine and d-amphetamine on response rate were generally independent of the control rate of responding. 相似文献
4.
Pre-exposure of rats to amphetamine sensitizes self-administration of this drug under a progressive ratio schedule 总被引:10,自引:8,他引:2
Two groups of male rats were tested to determine whether pre-exposure to d-amphetamine would enhance the motivation to self-administer the drug under a progressive ratio schedule of reinforcement.
In the first phase of the experiment, one group of rats received d-amphetamine (2 mg/kg IP), while a second group received saline on alternate days for a total of ten injections. Following
a 21-day drug withdrawal period, behavioral sensitization was confirmed by a significant increase in amphetamine-induced stereotypy
in the d-amphetamine-pretreated group, relative to the saline-pretreated group. In the second phase of the study, all rats were implanted
with chronic jugular catheters and trained to self-administer d-amphetamine (0.2 mg/kg per infusion) under a fixed-ratio schedule of reinforcement. The progressive ratio paradigm was then
imposed for 7 consecutive days; d-amphetamine-pretreated rats attained significantly higher break points than saline-pretreated animals. These data suggest
that pre-exposure to d-amphetamine may enhance the motivation to self-administer this drug.
Received: 16 July 1997 / Final version: 22 October 1997 相似文献
5.
Rationale: Prepulse inhibition of the startle reflex (PPI) is attenuated in animals after administration of d-amphetamine and other drugs that stimulate mesolimbic dopamine activity. Objective: The aim of the present study was to evaluate the effects of d-amphetamine (20 mg) on a variety of psychophysiological and subjective measures, including PPI, in humans. Method: Thirty-six participants (18 women) participated in a double-blind, placebo controlled, repeated measures study. In one session,
participants received d-amphetamine (20 mg) orally, and in the other session, participants received an identical appearing placebo. Participants
were assessed at 60, 90, and 120 min after ingestion with a 5-min block of startle trials (six control trials and six prepulse
trials) followed by subjective measures of stimulation and mood. Results: d-Amphetamine increased subjective measures of stimulation and euphoria, attenuated PPI, and increased heart rate, relative
to placebo treatment. Conclusions: The effect of d-amphetamine on the subjective measures was substantial and consistent over time, while the effect on PPI was only observed
at 90 min after ingestion, and the effect on heart rate was limited to 90 and 120 min after ingestion.
Received: 22 June 1998/Final version: 23 November 1998 相似文献
6.
Rationale
Agonist medications have been proven effective in treating opioid and nicotine dependence; results from clinical studies suggest that the indirect dopamine agonist d-amphetamine may reduce cocaine abuse. In preclinical studies, chronic d-amphetamine treatment decreased ongoing cocaine self-administration. 相似文献7.
Rationale. d-Amphetamine is a candidate agonist medication for the treatment of cocaine dependence, and evaluation of d-amphetamine effects on abuse-related effects of cocaine in preclinical assays is warranted.
Objective. This study was designed to assess the effects of chronic d-amphetamine treatment on cocaine- and food-maintained responding under a progressive-ratio schedule in rhesus monkeys. The
effects of schedule manipulations on cocaine and food-maintained responding were also examined for comparison with d-amphetamine effects.
Methods. Key-press responding under a progressive-ratio schedule resulted in the delivery of cocaine (0.032 mg/kg per injection) or
1 g food pellets. The effect of manipulating cocaine dose (saline, 0.001–0.1 mg/kg per injection) or the number of food pellets
delivered (0, 1 and 4 pellets) was determined. Subsequently, three schedule parameters were manipulated: (1) starting ratio
value, (2) increments of the ratio progression, and (3) duration of post-reinforcer time-outs when the ratio value was constant.
Finally, the effects of 10-day treatment with d-amphetamine (0.01–0.1 mg/kg per hour) were examined.
Results. Break points increased as a function of cocaine dose or the number of food pellets, and similar break points were maintained
by delivery of 0.032 mg/kg per injection cocaine and 1 food pellet. Manipulation of schedule parameters produced similar effects
on responding maintained by cocaine (0.032 mg/kg per injection) or food (1 pellet). In contrast, d-amphetamine produced a dose-dependent decrease in cocaine-maintained responding and had less consistent effects on food-maintained
responding.
Conclusions. These results are consistent with the hypothesis that chronic treatment with d-amphetamine decreases cocaine self-administration in rhesus monkeys, possibly by attenuating the reinforcing effects of cocaine.
Electronic Publication 相似文献
8.
Activation of 5-HT1B receptors in the nucleus accumbens reduces amphetamine-induced enhancement of responding for conditioned reward 总被引:2,自引:2,他引:0
Previously, we have demonstrated that 5-hydroxytryptamine (5-HT) injected into the nucleus accumbens attenuates the potentiating
effects of d-amphetamine on responding for conditioned reward (CR). The present studies examined the 5-HT receptor involved in this effect
by investigating the effects of 5-HT agonists with differing affinities for 5-HT1 and 5-HT2 receptors on d-amphetamine-induced potentiation of responding for CR. Rats were trained to associate a light/tone stimulus (subsequently
the CR) with water delivery. In a test phase, they were allowed access to a lever delivering the CR, and an inactive (NCR)
lever. Responding on the CR lever was greater than responding on the NCR lever, indicating that the light/tone stimulus functioned
as a CR. Responding for the CR was selectively potentiated by injections of d-amphetamine (10 μg) into the nucleus accumbens. This effect was reduced by injections into the nucleus accumbens of 5-CT
(0.5 and 1 μg), RU24969 (10 μg), CP93,129 (1.25 and 2.5 μg) but not by DOI (10 μg) or 8-OH-DPAT (5 μg). The lower doses of
5-CT and CP93,129 did not reduce baseline responding for CR, or responding for water in a separate group of animals, indicating
that the effects of these drugs were behaviourally selective. The higher doses abolished the CR effect, and in the case of
5-CT and RU24969 also reduced responding for water. All of the effective drugs share in common the ability to stimulate 5-HT1B receptors, albeit with differing selectivities. The effect of CP93,129, the most selective of the 5-HT1B agonists, to inhibit the response-potentiating effect of d-amphetamine was reversed by the5-HT1B/1D antagonist GR127935 (3 mg/kg). The results indicate that activation of 5-HT1B receptors within the nucleus accumbens attenuates the effects of a dopamine-dependent behaviour, and that activation of these
receptors can oppose the behavioural effects of elevated mesolimbic dopamine transmission.
Received: 22 April 1998/Final version: 28 July 1998 相似文献
9.
L. V. Panlilio Steven R. Goldberg Joanne P. Gilman Rebecca Jufer Edward J. Cone Charles W. Schindler 《Psychopharmacology》1998,137(3):253-258
The goal of this study was to determine whether slowly infused, response-independent cocaine would reduce cocaine self-administration
in an animal model of drug abuse. Seven male rhesus monkeys self-administered IV cocaine on a fixed-ratio 30 schedule (5-min
time-out). With unit dose (0.056 mg/kg per infusion for one monkey and 0.032 mg/kg per infusion for the rest) and infusion
volume (0.5 ml) held constant, the rate of delivery was manipulated (0.125, 0.1875, 0.375, 0.75 and 3 ml/min, with infusions
lasting 240, 160, 80, 40, and 10 s, respectively). Response rates increased monotonically as a function of delivery rate.
Responding for cocaine at the slowest delivery rate did not differ from saline. The effects of infusing additional cocaine
(starting 30 min prior to the session) at this non-reinforcing rate (0.125 ml/min) were then determined. Delivery rate of
the self-administered infusion was manipulated as before. Non-contingent cocaine significantly increased responding for cocaine
(at the fastest delivery rate) and for saline. While non-contingent cocaine reduced responding for cocaine in two of the seven
monkeys, it also significantly reduced responding in three monkeys that responded for food on the same schedule. Plasma levels
of cocaine delivered at rates of 0.125 and 3 ml/min were compared in five other monkeys. While a higher peak was reached with
the faster infusion, levels did not differ after 5 min. Thus, when an infusion became available (after the 5-min time-out)
in the self-administration experiments, plasma levels should not have differed regardless of the delivery rate. These results
suggest that a low-dose, slow-delivery treatment with cocaine might prime or reinstate drug seeking rather than decrease it.
Received: 1 July 1997 / Final version: 4 January 1998 相似文献
10.
Anne M. Birmingham Susan H. Nader Kathleen A. Grant Huw M. L. Davies Michael A. Nader 《Psychopharmacology》1998,136(2):139-147
2β-Propanoyl-3β-(4-tolyl)-tropane (PTT) is a cocaine analog which has been shown in rhesus monkeys to have cocaine-like discriminative stimulus
effects and a long duration of action (>8 h), yet does not function as a reinforcer when substituted for cocaine in monkeys
responding under a fixed-interval 5-min schedule (Nader et al. 1997). The purpose of the present study was to evaluate the
reinforcing effects of PTT under a fixed-ratio (FR) schedule and to determine if decreasing the inter-injection interval would
influence the reinforcing effects of PTT. Male rhesus monkeys (n=3) were trained to respond under a multiple FR 30 food-drug-food schedule. When responding was stable, cocaine (0.003–0.3 mg/kg
per injection) or PTT (0.001–0.03 mg/kg per injection) was available during the drug component for at least five consecutive
sessions and until stable responding was observed. To investigate whether the inter-injection interval would influence PTT-maintained
response rates, the time-out (TO) following PTT injections was reduced from 180 or 300 s to 10 s for at least five consecutive
sessions. Cocaine-maintained response rates were characterized as an inverted-U shaped function of dose, with peak rates maintained
by 0.03 mg/kg per injection cocaine. PTT (0.001–0.03 mg/kg per injection) maintained response rates significantly higher than
rates maintained by the PTT vehicle, but significantly lower than cocaine-maintained response rates; PTT intake increased
with dose. A reduction of the TO following PTT injections to 10 s did not alter PTT-maintained response rates or total session
intake. Self-administered PTT was more potent than cocaine at decreasing food-maintained responding. These results suggest
that for long-acting compounds like PTT, reinforcing effects are more likely to be observed when the drug is available under
a ratio-based schedule, compared to an interval-based schedule.
Received: 3 May 1997 / Final version: 11 October 1997 相似文献
11.
Rationale Psychostimulant drugs exert their behavioral effects primarily through enhancement of monoaminergic neurotransmission. Augmented
dopamine activity is thought to play a critical role in the psychomotor stimulant effects of amphetamine and cocaine, as well
as in the development of long-term behavioral sensitization evoked by repeated exposure to amphetamine. However, despite the
fact that brain dopamine and noradrenaline systems are closely interconnected, the extent to which noradrenergic transmission
contributes to these behavioral effects of psychostimulants is a relatively unexplored issue.
Objectives By inhibiting noradrenergic neurotransmission with the α2-adrenoceptor agonist clonidine, the α1-antagonist prazosin and the β-antagonist propranolol, we investigated the involvement of noradrenaline neurotransmission
in the psychomotor stimulant and long-term sensitizing effects of d-amphetamine and cocaine in rats.
Methods Clonidine (0.003–0.1 mg/kg), prazosin (0.1–3.0 mg/kg) and propranolol (1.0–3.0 mg/kg) were administered prior to d-amphetamine (1.0 mg/kg), cocaine (15 mg/kg) or apomorphine (1.0 mg/kg) and psychomotor activity was measured. In separate
studies, clonidine (0.03 mg/kg), prazosin (1.0 mg/kg) or propranolol (3.0 mg/kg) were co-administered with d-amphetamine (2.5 mg/kg) or cocaine (30 mg/kg) for 5 days, and locomotor sensitization was assessed 3 weeks post-treatment.
Results The psychomotor stimulant effect of d-amphetamine, but not that of cocaine or apomorphine, was dose-dependently inhibited by clonidine and prazosin, and enhanced
by propranolol. Clonidine, prazosin, and propranolol did not influence the induction of sensitization by amphetamine or cocaine.
Conclusions Enhancement of synaptic noradrenaline concentrations contributes to the psychomotor stimulant effect of d-amphetamine, but not cocaine or apomorphine. In addition, noradrenergic neurotransmission is not critically involved in the
induction of psychostimulant sensitization. 相似文献
12.
The present study investigated the effect of sensitization, induced by repeated injections of d-amphetamine, on sexual behavior in the naive male rat tested in a drug-free state. Injections of either d-amphetamine (1.5 mg/kg, IP) or saline were given every other day for a total of ten injections, and this regimen induced
behavioral sensitization of locomotor activity in drug-treated rats. After a 3-week post-drug period, d-amphetamine-treated rats exhibited facilitated sexual behavior, as indicated by shorter latencies to mount and intromit,
and a greater percentage of rats copulating. These rats also exhibited a general increase in the amount of copulation. Furthermore,
sensitized rats displayed a facilitated acquisition of sexual behavior (i.e. mount and intromission latency <300 s for 3 consecutive
days). After repeated sexual experience, rats pre-treated with d-amphetamine also showed an augmented increase in level changes made in anticipation of the presentation of a receptive female.
Finally, enhanced sexual behavior was independent of the environment in which repeated administration of d-amphetamine occurred, indicating that facilitation was not a consequence of conditioned associations between drug and test
environment. These results demonstrate that behavioral sensitization due to repeated psychostimulant administration can “cross-sensitize”
to a natural motivated behavior, such as sex. Furthermore, the subsequent facilitation of anticipatory sexual behavior (i.e.
level changes) after repeated experience in rats previously treated with d-amphetamine suggests that behavioral sensitization can influence incentive learning.
Received: 10 June 1998/Final version: 7 August 1998 相似文献
13.
Key pecking by pigeons was maintained under a 30-response fixed-ratio schedule of food delivery; lever pressing by squirrel monkeys was maintained under a 3-min fixed-interval schedule of food delivery. Administered alone, d-amphetamine (0.1–3.0 mg/kg), cocaine (1.0–3.0 mg/kg) and bupropion (1.0–30 mg/kg) either did not affect or decreased fixed-ratio responding of pigeons, whereas d-amphetamine (0.056–0.3 mg/kg) either increased or decreased (0.56 mg/kg) responding of monkeys maintained under the fixed-interval schedule. Prazosin, a selective centrally-active alpha1 antagonist, produced a dose-dependent reversal of the rate-decreasing effects of d-amphetamine and cocaine but not of bupropion on fixed-ratio responding in pigeons. Prazosin also reversed both the rate-increasing and rate-decreasing effects of d-amphetamine on fixed-interval responding of squirrel monkeys. In contrast, the non-selective alpha-antagonist phentolamine enhanced d-amphetamine-induced decreases in fixed-ratio responding. These findings suggest that the behavioral effects of d-amphetamine and cocaine are produced at least in part by activation of central alpha1 receptors. Prazosin may be a useful tool for better understanding the mechanisms through which cocaine, amphetamine, and other abused stimulant drugs exert their potent behavioral effects. 相似文献
14.
Rats were implanted with stimulating electrodes aimed at the medial forebrain bundle-lateral hypothalamus (MFB-LH) and were trained to lever-press for brain self-stimulation on a fixed interval: 60 s schedule of reinforcement. The effects of graded doses of naloxone (0.1–30 mg/kg), morphine (0.3–5.6 mg/kg), naloxone plus morphine,d-amphetamine (0.03–1.0 mg/kg), naloxone plusd-amphetamine, phencyclidine (0.3–5.6 mg/kg), and naloxone plus phencyclidine were tested. Naloxone produced a significant decrease in rates at 30 mg/kg. Naloxone (0.1–1.0 mg/kg) plus morphine blocked the dose-dependent decrease produced by morphine alone. In contrast, naloxone (1.0–10 mg/kg) plusd-amphetamine attenuated the graded increase in response rates produced byd-amphetamine. Naloxone (1.0–10 mg/kg) plus phencyclidine did not reliably change the increase in response rates produced by phencyclidine alone. The use of the fixed interval schedule of brain self-stimulation to study these drug interactions is novel, and further demonstrates that the highly reinforcing aspects of brain stimulation, known to be influenced by dopamine, may also be modulated by the endogenous opiate system. 相似文献
15.
D. E. McMillan 《Psychopharmacology》1982,78(2):131-134
Pigeons were trained to track the location of a red or green key color under a second order schedule, with reinforcement of responses to each color contingent upon whether 1.5 mg/kg phencyclidine (PCP) or saline had been administered before the session. When cumulative dose-effect curves were determined for other drugs substituted for PCP, pigeons responded predominantly on the PCP key after other doses of PCP, ketamine, pentobarbital, d-cyclazocine and l-cyclazocine, but not after saline, lactic acid solution, d-amphetamine, chlordiazepoxide, scopolamine, morphine, naltrexone, or d-, or l-methadone. l-Cyclazocine was slightly more potent than d-cyclazocine in producing PCP key responding. PCP key responding after the optical isomers of cyclazocine was not blocked by naltrexone. 相似文献
16.
The present study used a three-choice operant drug discrimination procedure to determine if NMDA-mediated discriminative
stimulus effects could be separated from other stimulus effects of 2.0 g/kg ethanol. Adult male Long-Evans rats (n = 7) were trained to discriminate dizocilpine (0.17 mg/kg; IG) from ethanol (2.0 g/kg; IG) from water (4.7 ml; IG) using food
reinforcement. Substitution tests were conducted following administration of the GABAA positive modulators allopregnanolone (5.6–30.0 mg/kg; IP), diazepam (0.3–10.0 mg/kg; IP) and pentobarbital (1.0–21.0 mg/kg;
IP), the non-competitive NMDA antagonist phencyclidine (0.3–10.0 mg/kg; IP), the 5-HT1 agonists TFMPP (0.3–5.6 mg/kg; IP) and RU 24969 (0.3–3.0 mg/kg; IP), and isopropanol (0.10–1.25 g/kg; IP). Allopregnanolone,
diazepam and pentobarbital substituted completely (>80%) for ethanol. Isopropanol partially (77%) substituted for ethanol.
Phencyclidine substituted completely for dizocilpine. RU 24969 and TFMPP did not completely substitute for either training
drug, although RU 24969 partially (62%) substituted for ethanol. Successful training of this three-choice discrimination indicates
that the discriminative stimulus effects of 0.17 mg/kg dizocilpine were separable from those of 2.0 g/kg ethanol. The finding
that attenuation of NMDA-mediated effects of ethanol occurred without altering significantly GABAA- and 5-HT1-mediated effects suggests that the NMDA component may be independent of other discriminative stimulus effects of 2.0 g/kg
ethanol.
Received: 18 November 1997 / Final version: 10 February 1998 相似文献
17.
Pigeons were trained to discriminate IM injections of 1.0 mg/kg d-amphetamine from water, 5.6 mg/kg pentobarbital from water, or 1.0 mg/kg d-amphetamine from 5.6 mg/kg pentobarbital by requiring them to peck different response keys depending on which substance was administered prior to the session. Excellent stimulus control was achieved under all conditions with close to 100% of the responses occurring on the injection-correlated key. In tests with doses different from those used in training, the percentage of responses on the drug key was directly related to drug dose. When d-amphetamine was given to birds trained to discriminate pentobarbital from water or when pentobarbital was given to birds trained to discriminate d-amphetamine from water, responding occurred predominately on the water-correlated key. d-Amphetamine produced a dose-related antagonism of the effects of pentobarbital for birds trained to discriminate pentobarbital from water or from d-amphetamine. Rates of responding on the drug key were generally highes after administration of the drug doses used in discrimination training; but response rates were not systematically related to the percentage of responses occurring on the drug key. All birds were subsequently trained to discriminate a combination of 1.0 mg/kg d-amphetamine and 5.6 mg/kg pentobarbital from either 1.0 mg/kg d-amphetamine or 5.6 mg/kg pentobarbital alone, demonstrating that the discriminative stimulus properties of amphetamine-pentobarbital combinations are different from either drug alone. Several of the drug effects reported were related to the drug discrimination that had been established.Portions of this paper were reported at the 49th annual meeting of the Eastern Psychological Association, Washington, D.C., 1978 相似文献
18.
Galen R Wenger 《Pharmacology, biochemistry, and behavior》1980,12(6):865-870
Pigeons were trained to respond under fixed-ratio 30 (FR30) schedules of grain presentation. The schedule consisted of two FR30 components. In one component, every 30th response produced access to grain; FR30. In the second component, every 30th response produced access to grain, but responding was suppressed by having every response produce a brief electrical shock; FR30 (shock). In one phase of the experiment, there were no visual stimuli associated with the separate components; mixed FR30 FR30 (shock), and in the second phase, a distinctive stimulus was associated with each of the two components; mult FR30 FR30 (shock). High rates of responding (~ 2.0 responses/sec) were maintained in the FR30 components, and responding was almost totally suppressed (<0.02 response/sec) in the FR30 (shock) components. The effects of phencyclidine and ketamine were compared with pentobarbital, d-amphetamine and morphine. Phencyclidine and ketamine, over a narrow dose range, produced small increases in responding under the FR30 (shock) component of both the mixed and multiple schedules. By comparison, pentobarbital produced very large increases in responding under the FR30 (shock) component of both schedules. Increasing doses of d-amphetamine and morphine either had no effect on or decreased the response rate in both components of the mixed and multiple schedules. The results suggest that phencyclidine and ketamine may have some properties qualitatively like pentobarbital and unlike d-amphetamine and morphine in attenuating the suppression of behavior produced by brief electrical shocks. 相似文献
19.
The influence of nicotine pretreatment on mesoaccumbens dopamine overflow and locomotor responses to D-amphetamine 总被引:2,自引:2,他引:0
Pretreatment with psychostimulant drugs causes sensitisation of their effects on locomotor activity and dopamine (DA) overflow
in the nucleus accumbens (NAcc) and there is evidence for similarities in the mechanisms involved. This study used in vivo
microdialysis in conscious freely moving rats to investigate the extent to which pretreatment with nicotine causes sensitisation
to D-amphetamine. Pretreatment with nicotine (0.4 mg/kg SC daily for 5 days) caused sensitisation of the locomotor responses to
D-amphetamine (0.1–0.5 mg/kg SC) but not cocaine (15 mg/kg IP). Nicotine pretreatment did not influence the increase in DA
overflow into dialysis probes, located in the core of the NAcc, evoked by systemic injections of D-amphetamine or cocaine (15 mg/kg IP) but decreased the overflow evoked by the administration of D-amphetamine (1 × 10–6 M) through the dialysis probe. The results provide further evidence for a dissociation between the expression of sensitised
locomotor responses to psychostimulant drugs and sensitisation of their stimulatory effects on DA overflow in the core of
the NAcc. The results suggest that the sensitisation of the effects of nicotine on DA overflow in this subdivision of the
NAcc may be pharmacologically specific to nicotinic drugs.
Received: 23 July 1997/Final version: 19 March 1998 相似文献
20.
Paul W Czoty Robert W Gould Jennifer L Martelle Michael A Nader 《Neuropsychopharmacology》2011,36(2):539-547
Chronic treatment with the indirect dopamine agonist d-amphetamine can reduce cocaine use in clinical trials and, in preclinical studies in laboratory animals, attenuates daily cocaine self-administration. The present study extended previous results to conditions designed to reflect a more clinically relevant experience of cocaine exposure and d-amphetamine treatment. Each morning, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio schedule of reinforcement. After determining a dose-response curve for cocaine (0.003–0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule of reinforcement in the evening, cocaine self-administration sessions were suspended and d-amphetamine (0.01–0.056 mg/kg/h, i.v.) was administered continuously for at least 24 days, except during cocaine self-administration sessions, which were conducted using the PR schedule once every 8 days. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was redetermined. Cocaine- and food-maintained responding were also examined after discontinuation of d-amphetamine. Although individual differences in sensitivity were observed, d-amphetamine produced selective, qualitatively similar decreases in the reinforcing strength of cocaine in all monkeys that persisted at least 4 weeks. Moreover, cocaine dose-effect curves were shifted downward and/or to the right. For 2 weeks following discontinuation of d-amphetamine treatment, the reinforcing strength of cocaine varied within and across individuals, however, on the whole no increased sensitivity was apparent. These data provide further support for the use of agonist medications for cocaine abuse, and extend the conditions under which such treatment is successful to those that incorporate clinically relevant patterns of cocaine use and drug treatment. 相似文献