摘要:

One difficulty in analyzing the molecular structure of behavior lies in reducing the data to a manageable size so that they can be described concisely but without a loss of important information. An approach to quantifying and comparing distributions of interresponse times (IRTs) and lever-press durations is described and then used to examine the acute effects of caffeine (an adenosine antagonist), cocaine, and three adenosine agonists in rats chronically consuming either tap water or water containing 1.0mg/ml caffeine. The adenosine agonists used were R(-)N6-(2-phenylisopropyl)adenosine [R-PIA (preferential A1receptor agonist)], 5'-(N-cyclopropyl)-carboxamidoadenosine [CPCA (preferential A2agonist)], and 5'-N-ethylcarbox-amidoadenosine [NECA (about equal agonist activity at A1and A2receptors)]. The rats' behavior was maintained under a Multiple Fixed-Interval (FI) 120 s, Duration > 5 s schedule of reinforcement. Under the FI schedule, the first lever-press after 120 s resulted in pellet delivery. Under the Duration > 5 s schedule, all lever-press durations greater than 5 s were reinforced. Molecular analyses of distributions of true IRTs (exclusive of lever-press durations) and lever-press durations were conducted by regressing percentiles of the distribution obtained from drug conditions against percentiles obtained from control conditions, a technique called empirical percentile—percentile analysis (or quantile-quantile analysis). The pattern of effects on response durations differed from that seen in IRTs. After acute administration of adenosine agonists, the distributions of lever-press durations under the FI schedule and subcriterion durations under the Duration > 5 s schedule were shifted rightward by a constant proportion, indicative of a generalized slowing of responding by these drugs. The effects of adenosine agonists on IRTs could be described by a power-function relationship whereby long IRTs were increased more than shorter ones. A rate-increasing dose of caffeine (10 mg/kg) did nothing to the molecular structure of lever-press durations or of IRTs, indicating that rate increases seen after this dose were due to an earlier onset of responding in the fixed-interval and were unaccompanied by disruptions in the physical execution of the response. The molecular structure of interresponse time distributions seen at the rate-decreasing dose of caffeine (60 mg/kg) resembled that of a rate-decreasing dose of cocaine, but not of the adenosine agonists. Both caffeine and cocaine produced a curvilinear relationship between drug and control percentiles such that very short IRTs were unaffected, but long ones were lengthened five- to 10-fold. This same dose of caffeine lengthened lever-press durations in a manner that resembled adenosine agonists but not cocaine. Percentile—percentile analyses reveal details about drug effects on the temporal structure of behavior and its physical execution that are not visible in molar analyses.

ISSN:0955-8810    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Many of the behavioral actions of caffeine are mediated by its blockade of adenosine receptors, a notion that may have implications for tolerance and supersensitivity associated with chronic caffeine exposure. To examine possible interactions between chronic caffeine and adenosine-related actions of several drugs, the acute effects of caffeine and three adenosine agonists on behavior maintained by a Multiple Fixed-Interval (FI), Duration > 5 s schedule of reinforcement were studied using rats chronically consuming either 0 (tap water control), 0.5 mg/ml, or 1.0 mg/ml of caffeine in their drinking water. 5'-(N-cyclopropyl)-carboxamidoadenosine [CPCA (preferential A2agonist)], 5'-N-ethylcarboxamidoadenosine [NECA (about equal agonist activity at A1and A2receptors)], and R(-)N6-(2-phenylisopropyl)adenosine [R-PIA (preferential A1agonist)], as well as caffeine (nonspecific adenosine antagonist), were administered acutely i.p. after behavior stabilized. Dose-related decreases in overall response rate were produced by all adenosine agonists. Acute administration of all adenosine agonists and higher doses of caffeine increased average lever-press durations under the FI schedule from about 0.3 s to between 1 and 3 s, a three- to 10-fold increase. CPCA and NECA were 10 times more potent than R-PIA on all measures. Caffeine increased overall response rate under the FI schedule at doses of 3–30 mg/kg in nontolerant rats, and decreased rates at higher doses, which also increased lever-press durations. Insurmountable tolerance was seen to the rate-increasing effects of caffeine on behavior under the FI schedule, in rats exposed chronically to caffeine. Modest evidence of surmountable tolerance was seen in the rate-decreasing effects on the Duration > 5 s schedule. No tolerance to increases in lever-press durations or decreases in response rates was detected. Chronic exposure to caffeine did not alter the acute effects of the adenosine agonists: on all measures and with all adenosine agonists, the dose—effect curves for the three caffeine-exposure groups were indistinguishable from one another. The relative potencies suggest that the acute actions of adenosine agonists are related to A2receptors. This is consistent with the failure to detect supersensitivity, since upregulation associated with chronic caffeine exposure appears primarily in A1receptors.

ISSN:0955-8810    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

This study examined the effects of differential outcomes on the speed of acquisition of a cocaine vs saline discrimination. Two groups of male Sprague-Dawley rats were trained to discriminate 8.0 mg/kg cocaine from saline. The experimental group was exposed to differential outcomes, where correct responses following the different injections (discriminative stimuli) were correlated with a particular outcome (either sweetened condensed milk or tap water). The control group received either sweetened condensed milk or tap water at random following cocaine and saline injections. Acquisition of schedule control and three progressively difficult testing criteria were examined. The differential outcomes group came under schedule control and reached the three progressively difficult testing criteria in significantly fewer sessions than the control group. To determine whether differential outcomes during training influenced the generalization to other doses of cocaine, substitution tests were administered with several other doses of cocaine (0.0–10.0 mg/kg) to both groups. Similar cocaine dose-response functions were observed with the differential outcome group and the control group and there was not a statistically significant effect of differential outcomes on the cocaine generalization curve.

ISSN:0955-8810    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

An animal's volitional consumption of ethanol may be influenced by both genetic and environmental factors. In addition, genetic control of ethanol intake may depend on the test paradigm used. In the present study, performance for, and intake of ethanol in a limited access oral operant paradigm, and preference for ethanol in a two-bottle free choice test in the home-cage were compared in female rats of the heterogeneous Sprague Dawley (SD) and inbred Lewis strains. A smaller proportion of SD rats reached criterion on the self-administration task (four of 10 SD vs eight of 10 Lewis), but those SD rats that did achieve criterion maintained higher levels of responding and greater ethanol intake, relative to the Lewis strain, in the operant self-administration paradigm. Additionally, SD but not Lewis rats exhibited increased locomotor activity and an increase in performance for ethanol compared with water. In marked contrast, Lewis rats exhibited a greater preference for 10% ethanol over water in the two-bottle choice test compared with the SD strain, which preferred water to ethanol. These results suggest that both genotype and test paradigm are involved in the extent to which ethanol serves as a positive reinforcer and that unlike two-bottle choice preference tests, self-administration studies are more highly predictive of the reinforcing properties of ethanol.

ISSN:0955-8810    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The purpose of this study was to examine, in healthy volunteers without histories of extensive sedative use, the acute behavioral effects of doses of alprazolam used in clinical applications. Subjects participated in daily sessions over 12 study days. They consumed a standard breakfast, received an oral drug dose (0, 0.25, 0.5, 1 mg) and completed performance tasks for 3 hours after dosing. Tasks included a digit-symbol substitution task, a repeated-acquisition of response sequences task, a differential reinforcement of low response rate task designed to monitor time estimation, a number recognition task, and a second-order repeated-acquisition of response sequences task. Each active dose was administered prior to two sessions, according to a randomized block design, and placebo sessions separated successive active-dose sessions. With the exception of the second-order repeated acquisition of response sequences task, dose-related changes in performance were observed during all tasks, but effects were significant only following the 1 mg dose. No drug-related changes were observed on visual-analog scale ratings of drug effect. The data indicate that the risk of adverse performance effects following use of alprazolam is related to dose, with risks increasing at doses at or above 0.5 mg.

ISSN:0955-8810    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The present studies examined the effects of intra-ventral tegmental area (VTA) injection of SCH 23390, a dopamine (DA) D1 receptor antagonist or 7-OH-DPAT, a DA D2/3 receptor agonist, on cocaine-stimulated motor activity. Intra-VTA SCH 23390 (1.5–15 nmol/side) dose-dependently blocked cocaine-induced motor activity. Thus, 15 nmol/side SCH 23390 completely blocked, while 5 nmol/side attenuated, the motor-stimulant response to cocaine. These doses of SCH 23390 did not alter basal motor activity, suggesting the effects on the motor-stimulant response to cocaine were not the result of a generalized suppression of activity. In contrast to previous studies, intra-VTA 7-OH-DPAT did not alter basal motor activity at any of the doses tested (0.5–15 nmol/side). In addition, intra-VTA 7-OH-DPAT (1.5–15 nmol/side) pretreatment did not significantly alter the motor-stimulant response to cocaine. These data suggest that DA D1 receptors in the VTA may play a role in psychostimulant-induced motor activity. However, the role DA D2/3 receptors in the VTA may have in cocaine-induced motor activity remains unclear.

ISSN:0955-8810    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Dose-dependent effects of 7-OH-PIPAT and PD-128,907 on motor behaviors and place conditioning were examined in rats. Four 2-day conditioning trials were conducted over 8 consecutive days. On one day of each trial, animals received an injection of either saline, one of six doses of 7-OH-PIPAT (0.01–10.0 mg/kg), or one of five doses of PD-128,907 (0.01–1.0 mg/kg), and were placed into a distinct compartment for 40 min. On the other day, animals received an injection of saline and were placed into a different compartment for 40 min. Locomotion, sniffing, and yawning were measured following the first and last drug injections. Place conditioning was assessed the day following the last conditioning trial. None of the doses of 7-OH-PIPAT or 0–0.3 mg/kg PD-128,907 produced place conditioning. However, 1 mg/kg PD-128,907 produced conditioned place preference (CPP). Across doses, both 7-OH-PIPAT and PD-128,907 produced a U-shaped change in sniffing and locomotion and an inverted U-shaped change in yawning. Across time, lower doses produced a decrease in sniffing and locomotion and an increase in yawning that were evident immediately, whereas higher doses produced a biphasic change in that there was an initial decrease followed by an increase in sniffing and locomotion. Behaviors produced by both low and high doses were sensitized following repeated administration. PD-128,907 produced CPP and was more potent than 7-OH-PIPAT in altering motor behaviors, possibly due to its greater selectivity for the D3 receptor.

ISSN:0955-8810    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

This study examined the effects of ethanol preloading on preference for tobacco cigarettes in 10 nicotine-dependent volunteers. The crossover, double-blind study involved pretreating participants with 0, 0.2, 0.4 or 0.8g/kg ethanol immediately prior to a task in which cigarettes and/or money could be earned. Tobacco cigarette preference was measured using the number of responses performed and reinforcers earned on a series of concurrent random-ratio schedules that yielded tobacco and money reinforcers. In addition to the preference measures, subjective effects and psychomotor performance were assessed before beverage ingestion and at regular intervals afterwards. Ethanol induced alterations in mood and psychomotor performance in a dose-related fashion. However, preference for tobacco cigarettes was not affected by ethanol pretreatment. The present study suggests that the increase in cigarette smoking that is associated with ethanol consumption does not involve changes in smokers' preference for cigarettes.

ISSN:0955-8810    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The effect of monetary contingencies on alprazolam self-administration was evaluated in seven male volunteers living in a residential laboratory. Drug administration occurred prior to an afternoon work session (13.00 h), and at the onset of an evening recreation period (17.30 h). On ‘sample’ days, participants were administered placebo or alprazolam (0.75 mg), and at the end of the afternoon work session, were told whether their task performance was ‘better’ or ‘worse’ than average. If they received ‘better’ feedback they earned 55, and if they received ‘worse’ feedback, they earned 15. On ‘choice’ days, participants chose to self-administer either alprazolam or placebo, with feedback occurring on two of the four choice days. Feedback was not actually linked to performance, but instead was pre-programmed. For one week, alprazolam administration was always associated with ‘better’ feedback on sample and choice days, and in the other week was associated with ‘worse’ feedback. When no feedback was delivered, alprazolam was self-administered equally often in the afternoon (57%) and evening (71%). When feedback was delivered, it significantly influenced the choice to self-administer alprazolam in the afternoon. ‘Better than average’ feedback resulted in alprazolam self-administration 57% of the time, but alprazolam self-administration decreased to 14% when it was associated with ‘worse than average’ feedback and reduced earnings. A similar pattern of effects has been reported ford-amphetamine. Thus, the self-administration of either a stimulant or a minor tranquilizer is significantly reduced when it is associated with a consequent loss of an alternative reinforcer, in this case money.

ISSN:0955-8810    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The effects of work requirement on human ethanol self-administration were systematically examined. Healthy volunteers with a history of moderate alcohol consumption (12 to 16 drinks per week) were recruited as subjects. Four subjects self-administered 4, 8 or 16% w/v ethanol solution contingent upon completion of a fixed-ratio (FR) response requirement. The ratio requirements were FR 32, FR 64 and FR 128 responses. Ethanol consumption at lower doses decreased with increases in FR. Ethanol consumption at the high dose was greatest across all ratio requirements and was unchanged by increases in the ratio requirement, indicating greater relative reinforcing effects of the high dose of ethanol. Ethanol consumption was sensitive to unit price with 53–82% of the variance explained by the unit price analysis.

ISSN:0955-8810    

出版商:OVID    

年代:1997

数据来源: OVID