摘要:

Previous studies found that animals trained to discriminate pentobarbital show a relatively inclusive generalization profile. They generalize to sedative‐hypnotics and anxiolytics, regardless of differences among such drugs in molecular mechanism of action. In contrast, animals trained to discriminate lorazepam have shown a generalization profile that appears selective for compounds with in‐vitro profiles as full agonists at the benzodiazepine modulatory site. The present study investigated whether benzodiazepine receptor ligands, to which pentobarbital‐trained rats had generalized under a two‐lever procedure, would occasion pentobarbital‐ or lorazepam‐appropriate responding when the rats were retrained to discriminate among pentobarbital, lorazepam and the no‐drug condition under a three‐lever procedure. A second group of rats was trained first to discriminate lorazepam and then retrained under the same three‐lever procedure. Under the two‐lever procedure, all pentobarbital‐trained rats showed dose‐dependent generalization to lorazepam, but not all lorazepam‐trained rats showed full generalization to pentobarbital. Both groups showed full generalization to diazepam and zaleplon, a novel hypnotic that is selective for α1‐subunit‐containing subtypes of the γ‐aminobutyric acid (GABA)Areceptor. Pentobarbital‐trained rats, but not all lorazepam‐trained rats, generalized to imidazenil. Under the three‐lever procedure, dose‐dependent generalization to lorazepam and pentobarbital was demonstrated on the appropriate levers. Diazepam shared discriminative effects with pentobarbital, zaleplon shared discriminative effects with lorazepam, and imidazenil shared discriminative effects with lorazepam and pentobarbital. These results show that when the opportunity for finer differentiation of discriminative effects of GABAergic drugs is provided, a generalization profile more in line with differential in‐vitro profiles can be revealed.

ISSN:0955-8810    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The purpose of this study was to determine whether progressive ratio (PR) schedules might provide additional information, as compared with fixed ratio or fixed interval schedules, on pharmacologic features of discriminative stimuli (e.g. stimulus intensity). Five pigeons discriminated between 5.6 mg/kg morphine and saline under an arithmetic PR5 schedule of food presentation. The final ratio before pigeons either stopped responding for 5 min or switched responding from the selected to the non‐selected key was designated as the last completed ratio (LCR). Pigeons responded 6.8% on the drug key following saline and 96.4% on the drug key following 5.6 mg/kg morphine. The average LCR value for saline was not significantly different from the average LCR value for morphine. A larger dose of morphine (10.0 mg/kg) increased the LCR value and significantly decreased rates of responding. Smaller doses of morphine (0.32 and 1.0 mg/kg) occasioned primarily saline‐appropriate responding and decreased LCR values. Buprenorphine substituted for morphine and significantly increased LCR values, whereas nalbuphine produced only partial (20–80%) morphine‐key responding and significantly decreased LCR. Cocaine did not substitute for morphine or modify LCR compared with saline control. Together, these results suggest that the stimulus effects of (μ‐opioids vary on a dimension (e.g. intensity) that can be quantified using PR schedules.

ISSN:0955-8810    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The administration of dizocilpine, a non‐competitiveN‐methyl‐d‐aspartate (NMDA) receptor antagonist acting at the associated ion channel, increased the grooming time induced in rats by the D1dopamine receptor agonist SKF 38393 and the stereotyped behaviour elicited by the D1/D2dopamine receptor agonist apomorphine, and reduced the locomotor response to the D2dopamine receptor agonist quinpirole. This supports the view that glutamate deficiency plays an important role in the pathogenesis of schizophrenia by altering the balance between glutamatergic and dopaminergic systems. Blockade of serotonin receptors counteracted the effect of dizocilpine on dopaminergic responses. Both the non‐selective 5HT1/5HT2antagonist methysergide, and ketanserin, which more specifically blocks 5HT2receptors, given at doses inhibiting serotonin‐mediated behaviours but which did not affect spontaneous motility and dopaminergic behaviours, hampered the dizocilpine‐induced potentiation of responses elicited by the stimulation of D1or D1/D2dopamine receptors and counteracted the dizocilpine‐induced reduction of hyperactivity observed following quinpirole administration. The results suggest that the functional integrity of the serotonergic system is fundamental for the occurrence of dopaminergic changes resulting from non‐competitive NMDA blockade.

ISSN:0955-8810    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The reinstatement of extinguished cocaine self‐administration behavior was studied in rats pretreated withN‐methyl‐d‐aspartate receptor antagonists. Rats were trained to self‐administer intravenous cocaine (0.32 mg/kg/infusion) during five consecutive daily sessions that were followed by five consecutive daily extinction sessions, during which cocaine was unavailable and cocaine‐associated cues (sound and light) were absent. Neither the competitiveN‐methyl‐d‐aspartate receptor antagonist d‐CPPene (0.3–3 mg/kg) nor the low‐affinityN‐methyl‐d‐aspartate receptor channel blocker memantine (1–10 mg/kg) reinstated extinguished responding. Priming injections of intravenous cocaine (Experiment 1), and exposures to cocaine‐associated stimuli (buzzer and light; Experiment 2) engendered responding on the reinforced lever in excess of that on the non‐reinforced lever. In Experiment 1, administration of d‐CPPene or memantine prior to the priming injection of cocaine eliminated the difference between reinforced‐lever and non‐reinforced‐lever response rates. For both d‐CPPene and memantine, however, this effect was largely due to increased responding upon the non‐reinforced lever rather than to decreased reinforced‐lever responding. In Experiment 2, d‐CPPene, but not memantine, abolished in a dose‐dependent manner the selective increase in reinforced‐lever over non‐reinforced‐lever responding that was induced by exposures to cocaine‐related stimuli. This effect of d‐CPPene was not due to increased non‐reinforced‐lever responding. These data help define the boundaries within whichN‐methyl‐d‐aspartate receptor antagonists can prevent reinstatement of cocaine‐seeking behavior (e.g. type of antagonist used and reinstatement procedure)

ISSN:0955-8810    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Lever pressing of rats was maintained in different chambers during two different sessions each day. At 0900 h, responding was maintained under a two‐component multiple schedule in which responses initiated an interval that had to elapse before delivery of food (time delay of 20 s and 40 s). In this schedule, a ‘response‐pause’ sequence preceded reinforcers, and acutely administered diazepam only decreased responding. At 1400 h, responding by the same subjects was maintained under a different two‐component multiple schedule, in which individual responses initiated an interval that had to be terminated by another response before delivery of food (DRL 20 s and 40 s). In this second schedule, a ‘response‐pause‐response’ sequence preceded reinforcers, and acutely administered diazepam increased responding. After studying the acute behavioural effects of diazepam during each separate ‘timing’ schedule, animals systematically received 1.7 mg/kg per day diazepam 2–5 min prior to their different schedule components, in order to study the influence of reinforcement contingency on the chronic effects of this drug. Diminution of the initial effects of diazepam during daily drug administration prior to DRL 20 s responding did not extend to DRL 40 s responding or to time‐delay responding, and tolerance did not develop at all for time‐delay responding. When diazepam was again administeredafterall the daily schedules for approximately 1 month, and then givenbeforethe individual DRL schedules, DRL responding was increased again as it had been prior to chronic drug administration. These results suggest that the behavioural effects of acutely administered diazepam are influenced by different ‘timing’ requirements, and that the behavioural effects of chronically administered diazepam are influenced by ‘timing’ requirements and by drug‐ and chamber‐related stimuli.

ISSN:0955-8810    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Polyamines are polycations present at high concentrations in the mammalian brain. We investigated the effect of an intrahippocampal infusion of spermidine, a polyamine agonist, immediately post‐training on the inhibitory avoidance learning paradigm in rats. Bilateral intrahippocampal microinjection of spermidine (0.02–20 nmol) caused an increase in test step‐down latencies at low concentrations. Administration of arcaine (0.002–0.2 nmol), an antagonist of theN‐methyl‐d‐aspartate (NMDA) receptor polyamine binding site, did not modify the test step‐down latencies. In contrast, co‐administration of arcaine and spermidine completely reversed the facilitatory effect of spermidine on the test step‐down latencies. These results provide evidence that polyamines may be involved in learning and memory modulation.

ISSN:0955-8810    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Alcohol consumption acutely increases smoking behavior, but the reverse relationship, the acute effects of smoking on alcohol intake, largely has been ignored. We examined whether smoking acutely increases the reinforcing value of alcohol, first in the absence of recent alcohol intake and then following an alcohol pre‐load. Healthy, social‐drinking smokers (n = 11 men, 14 women) engaged in a computerized task involving concurrent schedules of reinforcement for beer (FR10, 3 oz (90 ml) per reinforcement) or money (FR5 to FR30, $0.20 per reinforcement) during two sessions, one following day‐long ad lib smoking and the other following overnight smoking abstinence. During each session, subjects performed the task in two sets of trials, one before and one after consumption of an alcohol pre‐load, with 60 min between sets. To standardize the alcohol pre‐load, all subjects were led to believe that they had earned 9 oz (270 ml) of beer after the first trial set, which they then consumed before the second set of trials. Compared to responding during the abstinent session, responding for alcohol during the smoking session was no different before the alcohol pre‐load (trial set one) but was significantly greater following the alcohol pre‐load (trial set two), although only in men and not women. Subjective sedation after the alcohol pre‐load was attenuated during the smoking session in both men and women, but attenuated sedation due to smoking was related to subsequent alcohol‐reinforced responding only in men. Additional research is needed to determine the extent to which these effects in men are pharmacological in nature or are conditioned responses to smoking or to consuming a preferred alcoholic beverage.

ISSN:0955-8810    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The present experiment attempted to identify a substitute for cigarette smoking in a laboratory analog of the behavioral economics of drug dependence. The interaction between cigarette consumption and nicotine gum consumption was examined with eight human smokers by increasing the price of cigarettes (i.e. the number of responses required to obtain puffs) across sessions, while the price of concurrently available nicotine gum remained constant. In another phase, the price of nicotine gum was increased while the price of concurrently available cigarettes remained constant. To determine whether the presence of concurrently available nicotine gum influenced cigarette consumption, we also examined the effect of increasing the price of cigarettes on cigarette consumption without available nicotine gum. When cigarettes and nicotine gum were concurrently available, increases in the price of cigarettes increased consumption of nicotine gum. When the price of nicotine gum increased while the price of cigarettes remained constant, smokers nearly exclusively consumed cigarettes. The presence or absence of nicotine gum did not affect the relation between cigarette consumption and cigarette price. The results suggest that nicotine gum can maintain operant behavior of smokers in the laboratory and can function, in a behavioral economic sense, as a weak substitute for cigarette puffs. As a result, nicotine gum may be useful in human laboratory studies of the behavioral economics of reinforcer interactions and their role in drug dependence.

ISSN:0955-8810    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Järbe et al. (1998a)trained rats to discriminate between (−)‐Δ9‐tetrahydrocannabinol (Δ9‐THC) and vehicle, using different training doses in order to create assays with different efficacy demands, to examine whether (R)‐methanandamide, an analog of the endogenous ligand anandamide, had lower efficacy than Δ9‐THC. Rats were initially trained with 3 mg/kg Δ9‐THC, then tested with (R)‐methanandamide and Δ9‐THC. Thereafter, the rats were split into two groups and retrained with either 1.8 or 5.6 mg/kg Δ9‐THC, followed by additional tests with the two agonists. The current study systematically replicated this study in two groups of rats, trained from the outset to discriminate between vehicle and either 1.8 or 5.6 mg/kg Δ9‐THC, respectively. Two‐lever operant drug discrimination procedures were used. The outcomes in the two studies were similar. In tests with (R)‐methanandamide, full substitution occurred in the low‐dose Δ9‐THC training group, whereas substitution was partial in the high‐dose Δ9‐THC training group. (R)‐Methanandamide in higher doses exerted marked suppression of lever pressing. In tests with Δ9‐THC, full substitution occurred in both Δ9‐THC‐trained groups, and rates of responding were comparable to those observed during regular drug training sessions. In conclusion, both sets of data indicate that cannabinoid agonists either can have varying degrees of efficacy at a receptor site, or may produce their behavioral actions through multiple mechanisms, or both. Prevailing training‐dose condition rather than prior training‐dose history is the major determinant for the substitution pattern.

ISSN:0955-8810    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Six experienced cocaine smokers (two men, four women) participated in an inpatient study to compare self‐administration of smoked cocaine when either a $5 money or merchandise voucher was available as an alternative reinforcer. A six‐trial choice procedure was used, with sessions consisting of (1) one sample trial, where participants received the cocaine dose and the alternative reinforcer available that day, and (2) five choice trials, where participants chose between the available cocaine dose and the alternative reinforcer. There were eight sessions: in separate sessions, each dose of cocaine (0, 12, 25, 50 mg) was paired with a money voucher and with a merchandise voucher. The choice to self‐administer cocaine significantly increased with escalating cocaine doses, and significantly less cocaine was self‐administered when money vouchers were available as compared to merchandise vouchers. These data demonstrate that money vouchers are a more effective alternative reinforcer than merchandise vouchers in cocaine abusers.

ISSN:0955-8810    

出版商:OVID    

年代:2000

数据来源: OVID