摘要:

Altered motivation for drugs of abuse is a central feature of most definitions of drug dependence and the impact of drug‐related cues on motivation is of current interest. However, since most studies of cue‐reactivity have not used behavioural measures of motivation, their results are often difficult to interpret in motivational terms. In the current paper we describe two experiments in which a behavioural technique, based on multiple variable interval (VI) schedules of reinforcement, was used to study motivation for alcohol in human subjects. In both experiments, subjects attended for several sessions and, during each session, were exposed to a 6‐ply VI schedule (values ranged from 1 to 720 s), during which they earned points that were later exchanged for a preferred beer or lager. In Experiment 1 the procedure was validated by showing that changes in the magnitude of reinforcement altered behaviour appropriately. In Experiment 2 we found evidence that the presence of an alcohol‐related cue increased the value of alcohol rewards. The results are discussed with reference to a model for the behavioural effects of drug‐related cues in triggering relapse and a number of problems we found in using the multiple variable interval schedule procedure.

ISSN:0955-8810    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Although punishment contingencies are widely used with human drug users, basic research on the effectiveness of these procedures is limited. The present study evaluated the effects of a negative punishment contingency, response‐contingent timeout (TO) presentation, on cocaine‐maintained responding. Rhesus monkeys were trained under a multiple fixed interval (FI) 5‐min cocaine, conjoint FI 5‐min cocaine‐variable‐interval (VI) 30‐sec TO schedule. TO values were either 0 (baseline), 10, 30, or 60 s in length. During the TO periods, the FI clock continued to operate but the discriminative stimuli signaling cocaine availability were removed, and responding had no scheduled consequence. Cocaine maintained responding in all monkeys and the dose–effect curve was characterized as an inverted U‐shaped function. The response‐contingent TO presentations reduced response rates maintained by cocaine in all monkeys compared to baseline. The magnitude of the reduction in response rates was not a function of the length of the TO period (i.e. intensity of the punisher), and the punishment effect was enhanced by increases in cocaine dose. When responding was punished, response rates in the unpunished components either also decreased (i.e. response induction; ∼30% of the cases) or were not affected (∼60%). These results demonstrate that cocaine‐maintained behavior can be decreased by environmental manipulations involving negative punishment contingencies.

ISSN:0955-8810    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Repeated administration of morphine to rats increases their sensitivity to behavioral effects of morphine as well as to those of psychomotor stimulants, such as cocaine and amphetamine. Conversely, stimulant‐induced sensitization to behavioral effects of stimulants often results also in sensitization to behavioral effects of morphine. However, in nigrally lesioned rats, repeated injections of morphine produce sensitization to morphine‐induced turning but not to turning induced by cocaine or amphetamine. The present study was performed to determine whether giving repeated cocaine injections to nigrally lesioned rats would produce cross‐sensitization to morphine‐induced turning. Daily injections of 10 mg/kg cocaine (i.p.) enhanced the turning response to cocaine by day 8, but not the turning response to 3.0 mg/kg morphine (s.c.). The response to morphine increased equally in both cocaine‐ and saline‐treated animals after they had received morphine once. Dose–response curves for morphine (1.0–10 mg/kg) and for cocaine (3.0–30 mg/kg), determined during weeks 3 and 4, were the same in rats receiving daily injections of cocaine or daily injections of saline. Thus, although repeated exposure to cocaine or morphine resulted in sensitization to turning induced by each drug, respectively, there was no cross‐sensitization between the two drugs. In contrast to other behaviors, rotational behavior does not seem to exhibit cross‐sensitization between morphine and psychomotor stimulants.

ISSN:0955-8810    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Recent studies have shown that antagonists of serotonin (5‐HT)1Breceptors attenuate cocaine‐induced locomotor hyperactivity, whereas agonists enhance reinforcing and discriminative stimulus effects of the psychostimulant. The present study was designed to determine how 5‐HT1Breceptor ligands affected the development or the expression phase of sensitization to the cocaine‐induced locomotor response in rats. In Experiment 1, rats were treated repeatedly (for 5 days) with cocaine (10 mg/kg) in combination with either saline, GR 127935 (5‐HT1Bantagonist), CP 94,253 (5‐HT1Bagonist) or GR 127935 + CP 94,253. On day 10, they received a challenge dose of cocaine (10 mg/kg). In Experiment 2, animals received either saline or cocaine (10 mg/kg) for 5 days, and were then challenged with cocaine (10 mg/kg) in combination with saline, GR 127935, CP 94,253 or GR 127935 + CP 94,253, on day 10. In Experiment 3, rats received either saline, cocaine or CP 94,253 for 5 days; on day 10 they received challenge doses of CP 94,253 or cocaine. In rats treated repeatedly with cocaine, the locomotor hyperactivity induced by a challenge dose of the psychostimulant was about twice as high as that observed after its first administration. The effect evoked by cocaine challenge was further increased in animals treated repeatedly with CP 94,253 + cocaine, but not with GR 127935 + CP 94,253 + cocaine. No difference was observed in the response to cocaine challenge in rats treated repeatedly with cocaine or GR 127935 + cocaine (Experiment 1). In animals treated repeatedly with the psychostimulant, the behavioral response to a challenge dose of cocaine was dose‐dependently increased when that drug was combined with CP 94,253, but not with GR 127935 + CP 94,253. No difference was observed in the locomotor response of rats challenged with cocaine or GR 127935 + cocaine (Experiment 2). When rats were treated repeatedly with cocaine, a challenge dose of CP 94,253 produced an about threefold increase in the locomotor effect compared to the animals treated likewise with saline (Experiment 3). Our results indicate that 5‐HT1Breceptors are involved in neither the development nor the expression of sensitization to cocaine‐induced locomotor hyperactivity. On the other hand, they also show that pharmacological activation of 5‐HT1Breceptors enhances both phases of this phenomenon, and that repeated administration of cocaine leads to an increased functional reactivity of these receptors.

ISSN:0955-8810    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Groups of rats were exposed to daily, 3‐h, fixed‐time 1‐min food‐pellet delivery sessions, a procedure that produces overdrinking (schedule‐induced polydipsia, SIP). Previous research demonstrated that rats drinking a drug or non‐drug solution come to prefer that solution to water if the solution had (a) a past association with either a highly acceptable vehicle (e.g. glucose/saccharin), or (b) allowed rats to eschew drinking an unacceptable solution under SIP conditions. The present experiments show that under the solution‐avoidance procedure, preference for a concurrent, alternative solution (0.19 mg/ml lidocaine or 0.24 mg/ml cocaine) occurred when a concentrated quinine solution alternative was either abruptly removed or faded. A concentrated cocaine solution, however, was minimally effective in producing a preference for 0.19 mg/ml lidocaine to water when cocaine concentration was faded. Flavor/nutrient‐conditioning (conditioned reinforcement) and solution‐eschewing (avoidance) procedures may throw light on the kinds of historical situations that determine the genesis of stable preferences for drugs and other substances.

ISSN:0955-8810    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The present investigation examined sensitivity to the effects of various sedative–hypnotics on motor performance in rats treated chronically with phenobarbital. Eight rats were trained to walk on a rotorod treadmill at low (8 r.p.m.) and high (24 r.p.m.) rotational speeds. Prior to the chronic regimen, phenobarbital, pentobarbital, amobarbital, diazepam and clonazepam produced dose‐dependent impairments in motor performance at both speeds. During chronic treatment with phenobarbital (100 mg/kg/day), tolerance was conferred to the effects of all the drugs examined, as evidenced by rightward shifts in their dose–effect curves. For all drugs, the magnitude of this tolerance was generally consistent across the two speeds. Following a 6‐week washout period, during which no drugs were administered, dose–effect curves for each drug shifted back toward their original (i.e. pre‐chronic) positions. Under all conditions, the doses required for each drug to impair motor performance at the low speed were higher than those required to impair motor performance at the high speed. These data suggest that sensitivity to the motor‐impairing effects of sedative–hypnotics is influenced by the difficulty of the behavioral task, but that task difficulty does not modulate the maximal extent to which tolerance and cross‐tolerance are expressed.

ISSN:0955-8810    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Sensitization to the rate‐decreasing effects of opioid antagonists induced by acute pretreatment with opioid agonists has been suggested to reflect initial changes in opioid systems that underlie physical dependence. Glutamate receptors are implicated in the development and expression of opioid dependence, and antagonists acting at theN‐methyl‐ d ‐aspartate (NMDA) subtype of glutamate receptors have been shown repeatedly to attenuate the severity of opioid withdrawal. The present study evaluated the ability of a competitive NMDA receptor antagonist, d ‐CPPene (SDZ EAA 494; 3‐(2‐carboxypiperazin‐4‐yl)‐1‐propenyl‐1‐phosphonic acid), to affect morphine‐induced sensitization to naloxone in rats trained to lever‐press on a multiple‐trial, fixed‐ratio 10 schedule of food reinforcement. d ‐CPPene (0.3–3 mg/kg) was administered either 4 h or 30 min prior to the test session. Morphine (10 mg/kg) or its vehicle was administered 4 h before naloxone challenge (0.3–3 mg/kg). d ‐CPPene failed to prevent morphine‐induced potentiation of the naloxone‐produced decrement in operant performance. Thus, these results suggest that agonist‐induced sensitization to behavioral effects of opioid antagonists may be insensitive to NMDA receptor blockade.

ISSN:0955-8810    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Dopamine (DA) receptor blockade induces catalepsy in rats which increases in strength upon retesting. This increase in catalepsy represents a form of sensitization which has been shown to be completely context dependent. Sensitization of catalepsy therefore represents a good model for studying the neurobiological mechanisms underlying the interaction between the cellular effect of a drug (DA‐receptor blockade) and the context. This study investigated whether glutamatergic mechanisms are involved in the development of sensitization. Rats were treated with either haloperidol or haloperidol plus anN‐methyl‐ d ‐aspartate (NMDA) receptor antagonist. Haloperidol consistently induced catalepsy which developed sensitization upon retesting. Co‐administration of d‐ CPPene (5 mg/kg and 10 mg/kg, i.p.), eliprodil (30 mg/kg, i.p.) or Ro 25‐6981 (15 mg/kg, i.p.) did not have any effect on sensitization, although all three drugs exerted some anticataleptic effects. When sensitization developed under haloperidol plus NMDA receptor antagonist, the sensitized response was expressed only in the presence of the NMDA receptor antagonist. This strongly suggests that the NMDA receptor antagonists represent contextual stimuli to which catalepsy has been conditioned, and this implies that the expression of sensitization has been rendered state‐dependent.

ISSN:0955-8810    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0955-8810    

出版商:OVID    

年代:2001

数据来源: OVID