Tolerance to discriminative stimulus effects of d-amphetamine.

Chronic administration of high doses of d-amphetamine produced time-limited, surmountable tolerance to stimulus effects of d-amphetamine. 23 male Sprague-Dawley rats discriminated saline and 0.80 mg/kg d-amphetamine under fixed ratio (FR) schedules of food delivery. Suspending training and administering saline did not alter sensitivity to d-amphetamine, indicating that neither tolerance nor sensitization developed during regular training. Acute pretreatment with 3.2 mg/kg d-amphetamine did not alter the ED50 for stimulus effects of d-amphetamine. In contrast, administration of 3.2 or 6.4 mg/kg d-amphetamine, b.i.d., for 3 days or 2 weeks increased the ED50 for stimulus effects 3- to 4-fold but did not produce consistent tolerance to rate-altering effects. Tolerance to stimulus effects was surmountable, as higher doses of d-amphetamine produced full drug-lever selection in tolerant rats. Sensitivity recovered after chronic administration ended. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinstatement of orienting behavior by d-amphetamine in rats with superior colliculus lesions.

Assessed the involvement of the nigrotectal pathway in the expression of visual orienting behavior by a combination of superior colliculus (SC) lesions and increased dopamine transmission produced by administration of dextroamphetamine (1 mg/kg, intraperitoneally [ip]), using 60 naive male Long-Evans rats. Orienting behavior elicited by apparently moving or stationary light displays, its habituation, and recovery were observed. In intact Ss, amphetamine injections had a small but reliable effect on the habituation of orienting behaviors. Ss with SC lesions did not orient to the lights. Amphetamine-injected Ss with SC lesions did orient, and the topography of their orienting behavior, rate of habituation, and recovery of orienting with changes in the light display were comparable to those of the intact S. Results suggest a view of SC-lesion-impaired orienting behavior as a disturbance of sensory attention and emphasize the interaction of the SC and other neural systems in processes mediating the direction of attention. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of tail-pressure stress and d-amphetamine in disruption of the rat's ability to ignore an irrelevant stimulus.

48 male Sprague-Dawley rats received either 0 or 30 preexposures to a tone that was later used as a warning stimulus in a 2-way active avoidance task. Consistent with previous data, tone preexposure resulted in retarded acquisition of the conditioned avoidance response (CAR) in saline-control Ss and in Ss that received chronic administration of dextroamphetamine (DAM; 1 mg/kg, sc). Ss that received tail-pressure stress prior to stimulus preexposure also showed retarded acquisition of the CAR. However, Ss that received a combination of tail pressure and DAM did not show retarded CAR acquisiton following stimulus preexposure. Results suggest an interaction between environmental stressors and DAM in producing attentional deficits. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A three-choice discrimination procedure dissociates the discriminative stimulus effects of d-amphetamine and (±)-MDMA in rats.

(±)-3,4-Methylenedioxymethamphetamine (MDMA) produces subjective effects in humans that are similar to, but distinguishable from, those of psychostimulants. Drug discrimination studies in nonhumans have yielded inconsistent results regarding the similarities between MDMA and the psychomotor stimulant d-amphetamine. This study successfully used a 3-choice operant procedure to establish MDMA and d-amphetamine as discriminative stimuli in rats. Cocaine produced complete substitution for d-amphetamine, and LSD produced dose-dependent increases in MDMA-appropriate responding with nearly complete substitution (78%) for MDMA. The hallucinogen 2,5-dimethoxy-4-bromoamphetamine only partially substituted for MDMA and severely disrupted response rate. Fenfluramine, 3,4-methylenedioxyamphetamine-hydrochloride([+]-MDA), and (-)-MDA all produced complete substitution for MDMA. The serotonin-receptor antagonist pirenpirone only partially blocked MDMA discrimination. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttrial d-amphetamine sulfate and one-trial learning in mice.

Conducted 3 experiments with a total of 216 male albino LACA mice to investigate the effect of dextroamphetamine sulfate on memory in such a way that (a) state-dependency learning effects were excluded, (b) the time of learning was known rather precisely, (c) the drug might be introduced rapidly after the learning trial if recovered, and (d) no previous learning experience or drug effects would be present to confound the interpretation of results. Results show that amphetamine (2 mg/Kg, iv) immediately after footshock on a 1-trial passive avoidance learning task impaired performance in retention tests 24 and 96 hrs later. When the injection was delayed by as little as 90 sec, no such impairment was seen. A similar injection immediately after the learning trial of a water-rewarded 1-trial appetitive task had no discernible effect on performance in retention trials 24 hrs and 6 wks later. It is argued that the effects of the amphetamines on learning behavior depend on whether reward or punishment is involved and, further, that all such effects could be accounted for in terms of the drugs' influence on memory mechanisms. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of d-amphetamine on task performance and social behavior of humans in a residential laboratory.

Six healthy adult male volunteers lived for 11 days in a residential laboratory. Acute effects of d-amphetamine (0, 5, or 10 mg/70 kg) on performance of tasks, social interaction, and self-reports of drug effects were measured. Each day, participants engaged in a 6.5-hr work period and a 6.5-hr recreation period. Beverages containing d-amphetamine or placebo were consumed daily before the work period and before the recreation period. d-Amphetamine increased response rate without affecting accuracy on some tasks. d-Amphetamine increased the proportion of time spent engaging in verbal interaction during the first but not the second week of the study. No changes in self-reported drug effects were observed. Thus, d-amphetamine improved performance in the absence of stimulant-like subjective effects. This differentiation between performance and subjective effects confirms the importance of determining the effects of drugs on a range of behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of d-amphetamine and smoking abstinence on cue-induced cigarette craving.

In this study, the authors investigated the effects of the indirect dopamine agonist d-amphetamine (AMPH) on cue-induced cigarette craving in smokers. Abstinent or nonabstinent cigarette smokers (N=21) rated their cravings for cigarettes and for food (control) after pretreatment with AMPH (15 mg) or placebo and before and after viewing blocks of smoking-related, food-related, and neutral pictures. Before the cues were presented, AMPH increased cigarette craving and decreased food craving. Smoking and food cues increased craving for cigarettes and for food, respectively. AMPH also further increased cigarette craving (and decreased food craving) after cue presentation, but it did so regardless of cue type (food or smoking). Smoking abstinence markedly increased craving regardless of cue presentation or drug condition. These results suggest that both AMPH and smoking abstinence can increase cigarette craving, but they do not appear to specifically affect responses to conditioned smoking-related cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A verification of psychostimulant-induced improvement in sustained attention in rats: Effects of d-amphetamine, nicotine, and pemoline.

Previous studies from this laboratory have demonstrated that a variety of psychostimulant drugs can improve the performance of rats trained in a 2-choice stimulus detection task in which the correct responses are indicated by a briefly illuminated light. To enhance the construct validity of the task for assessing sustained attention, the procedure was modified so that the precue interval across trials varied unpredictably between 3, 7, and 11 s. After training rats (N?=?17) so that their baseline accuracy levels stabilized between 75% and 88% correct, their performance was assessed after administration of d-amphetamine (0.125–0.75 mg/kg sc), nicotine (0.25–0.75 mg/kg sc), and pemoline (5.0–30.0 po). At certain doses all 3 drugs induced performance improvements in mean choice accuracy and choice response time. Because the precue intervals varied unpredictably and the cue durations used to maintain the rats' baseline accuracy levels were typically short (range/&=/&70–500 ms), the task conforms to most conditions typically required for assessing sustained attention. Results verify the proposal that psychostimulant drugs can enhance the attentiveness of animals in a fashion similar to that documented in humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Personality factors moderate subjective and psychophysiological responses to d-amphetamine in humans.

The aim of the present study was to examine the relationship between measures of novelty and sensation seeking and both psychophysiological and subjective measures of stimulation after a pharmacological challenge with an indirect dopamine agonist, d-amphetamine. Prepulse inhibition (PPI) of the startle reflex and subjective responses were assessed after the challenge. The results indicated that the Novelty Seeking scale of the Tridimensional Personality Questionnaire (TPQ; M. Zuckerman, 1994). TPQ was a significant predictor of lower PPI and greater subjective stimulation. The Disinhibition scale of the Sensation Seeking Scale (SSS; M. Zuckerman, S. B. G. Eysenck, & M. J. Eysenck, 1978) moderated the effects of amphetamine on stimulation and elation, whereas the Boredom Susceptibility and Experience Seeking subscales of the SSS moderated subjective stimulation. These findings indicate that higher scores on novelty and sensation seeking correspond to heightened sensitivity to the effects of a stimulant medication. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of d-amphetamine and strychnine on cycloheximide- and diethyldithiocarbamate-induced amnesia in mice.

Administered cycloheximide (CXM) sc to groups of C57BL/6J mice 30 min before or immediately after training on a passive avoidance task and tested them 72 hrs later. Some CXM-pretreated groups were given strychnine or dextroamphetamine immediately after training and others were given amphetamine 1 hr after training. Other groups were given diethyldithiocarbamate (DDC) at various times before or after training. Some DDC-pretreated groups were given amphetamine or strychnine as described above for CXM groups. Immediate posttraining administration of 5 mg/kg amphetamine, but not strychnine, prevented amnesia in CXM-pretreated Ss. DDC induced an apparent amnesia when administered from 30 min before training to 3 hrs after training. Posttraining administration of amphetamine or strychnine did not prevent DDC-induced amnesia. Results are discussed in relation to previous suggestions that CXM and DDC-induced amnesia may be the result of a functional impairment of catecholamine neurotransmitter systems by these drugs. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dextromethorphan potentiation of d-amphetamine-induced behavior and neurodegeneration in rats.

Dextromethorphan ([DXM] 25–200 mg/kg/day) potentiated the behavioral and toxic effects of d-amphetamine sulfate ([DAS] 7–35 mg/kg/day). 66 male rats were administered these drugs alone and in combination continuously for 2 days. DXM shifted DAS-induced behaviors to resemble higher dose behaviors, though there was no dose effect of DXM. DXM increased the incidence of neurodegeneration in the neostriatum and the cerebral cortex (determined histologically) at every dose of DAS. These effects may have been related to the known antagonistic actions of DXM on voltage-dependent calcium channels or on N-methyl-D-aspartate (NMDA) receptors or may have involved alteration of amphetamine metabolism through interactions with the cytochrome P-450 enzyme, CYP2D6, for which both DXM and DAS are ligands. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of genotype and postnatal experiences on activity, avoidance, shock threshold, and open-field behavior of rats.

Studied the effects of postnatal experience in 6 experiments on the activity, avoidance, shock threshold, and open-field behavior of 91 selectively-bred Ss from high-avoidance (RHA/Lu) strains and 93 from low-avoidance (RLA/Lu) strains. Significant differences were found between postnatal experiences in shuttle box activity, but strain differences were not significant. The high-avoidance Ss acquired avoidance learning significantly faster and had lower shock thresholds than the low-avoidance Ss. However, postnatal experience had significant effects on avoidance and shock threshold only in the high-avoidance Ss. No significant strain differences were found in open-field behavior, and the postnatal experience effects showed only higher order significant interactions. Results are discussed in the framework of quantitative genetics and a direct-action hypothesis of postnatal experience. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of unconditioned stimulus escape and avoidance in discriminative avoidance learning in the gerbil (Meriones unguiculatus).

Gave separate groups of male gerbils (N = 80) shuttle-avoidance training or classical trials (CS and UCS pairings) in a 100-trial session. The shock UCS was either escapable or inescapable (i.e., of fixed duration-.1-3.0 sec). CRs, intertrial interval responses, and observations of the Ss' reactions to each UCS were recorded. Avoidance learning emerged only in groups exposed to escapable shock or a brief inescapable shock. Based on both the observational data of the nature of the shock-elicited reactions and shuttle performance, it is concluded that response termination of the UCS is not necessary for shuttle-avoidance learning. Results are discussed in terms of a punishment theory of avoidance and the species-specific defense-reaction hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Glossopharyngeal nerve transection impairs unconditioned avoidance of diverse bitter stimuli in rats.

There is growing evidence of heterogeneity among responses to bitter stimuli at the peripheral, central and behavioral levels. For instance, the glossopharyngeal (GL) nerve and neurons receiving its projections are more responsive to bitter stimuli than the chorda tympani (CT) nerve, and this is particularly true for some bitter stimuli like PROP & cycloheximide that stimulate the GL to a far greater extent. Given this information, we hypothesized that cutting the GL would have a greater effect on behavioral avoidance of cycloheximide and PROP than quinine and denatonium, which also stimulate the CT, albeit to a lesser degree than salts and acids. Forty male SD rats were divided into four surgery groups: bilateral GL transection (GLX), chorda tympani transection (CTX), SHAM surgery, and combined transection (CTX + GLX). Postsurgical avoidance functions were generated for the four bitter stimuli using a brief-access test. GLX significantly compromised avoidance compared to both CTX and SHAM groups for all stimuli (p     

Aripiprazole as a potential pharmacotherapy for stimulant dependence: Human laboratory studies with d-amphetamine.

Amphetamine and cocaine dependence present significant public health concerns, yet no broadly effective pharmacotherapy for stimulant dependence has been developed. Two human laboratory studies are reviewed that tested the ability of aripiprazole, a novel antipsychotic with partial agonist activity at D2 dopamine receptors, to alter the behavioral effects of stimulants using d-amphetamine as a model agent. In each of these experiments, volunteers learned to discriminate 15 mg d-amphetamine (i.e., ≥80% drug-appropriate responding over 4 consecutive sessions). The effects of a range of doses of d-amphetamine (0, 2.5, 5, 10, and 15 mg) were then tested alone and following pretreatment with aripiprazole (20 mg in Experiment 1; 10 mg in Experiment 2). In Experiment 1, aripiprazole (20 mg) attenuated the discriminative stimulus and many of the subject-rated effects of amphetamine. Aripiprazole alone produced performance decrements. To determine whether a lower dose of aripiprazole would also attenuate the behavioral effects of d-amphetamine without impairing performance, Experiment 2 was conducted. Aripiprazole (10 mg) failed to alter the discriminative-stimulus effects but attenuated some of the subject-rated effects of d-amphetamine. This dose of aripiprazole did not impair performance. The results of these experiments indicate that aripiprazole may have clinical utility in treating stimulant dependence. Future human laboratory research should better model the clinical use of aripiprazole by examining the effects of chronic aripiprazole combined with either methamphetamine or cocaine in dependent individuals. A large-scale clinical trial is also needed to evaluate the efficacy of aripiprazole for the treatment of stimulant dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Species-specific behavior and acquisition of avoidance behavior in rats.

Studied thigmotaxis (i.e., the tendency to run in contact with objects) in 3 experiments with a total of 54 female Long-Evans rats. Exp. I indicated that Ss became more thigmotactic and immobile following shock compared with no-shock conditions. Exp. II demonstrated that when 2 groups were required to make comparable, but different, avoidance responses, the group whose avoidance response was more closely related to the S's species-specific defensive behavior was acquired at a faster rate. The 3rd experiment indicated that the differences in the acquisition of the avoidance responses in Exp. II were not due to differences in operant rates for the 2 responses per se, since acquisition of these same 2 responses was similar under appetitive motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation of appetitive Pavlovian conditioning by d-amphetamine in the shell, but not the core, of the nucleus accumbens.

The effects of postsession d-amphetamine within subregions of the ventral and dorsal striatum on appetitive Pavlovian learning were assessed. Rats acquired a conditioned approach response on presentation of a stimulus predictive of 10% sucrose solution (unconditioned stimulus [US]), but not during equally frequent presentations of a stimulus uncorrelated with the US. In Experiment 1, postsession d-amphetarnine infusions enhanced acquisition of conditioned responding, with no effect on control measures. In Experiment 2, rats received postsession d-amphetamine in the accumbens shell or core. Shell infusions facilitated conditioning; core infusions did not. In Experiment 3, dorsomedial striatal infusions of d-amphetamine also were ineffective. In sum, dopaminergic activation within the shell, but not the core, of the nucleus accumbens facilitates the acquisition of a Pavlovian association. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of variations in stimulus similarity and response requirement during pre-shock upon subsequent one-way active avoidance learning.

Describes 2 experiments with 48 adult male Holtzman albino rats, which examine further the stimulus and response conditions under which prior fear conditioning facilitates 1-way active avoidance acquisition. Fear in both experiments was established during passive avoidance training by administering a single 2-sec shock following a cross-through response from a white to a black compartment. Subsequent active avoidance acquisition was facilitated in Exp. I even though the response requirements of the 2 tasks were incompatible. In Exp. II reversed stimulus-shock arrangements existed in the 2 learning tasks. Facilitation of avoidance acquisition as a function of the prior task was again obtained. (French summary) (15 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Elevated levels of impulsivity and reduced place conditioning with d-amphetamine: Two behavioral features of adolescence in mice.

Human adolescents may have experience with easily available psychoactive drugs. Impulsivity and/or peculiarities in reward systems may play a role. These variables were studied in adolescent (Postnatal Day [PND] 30-49) and adult (PND > 60) CD-1 mice. In Experiment 1 (impulsivity), food-restricted mice were tested in operant chambers with 2 nose-poking holes that delivered 1 food pellet immediately or 5 pellets after a delay, respectively. Delay length was increased over days (0-100 sec). Adolescent mice showed a shift to the left in the intolerance-delay curve, as well as enhanced demanding when nose-poking was not reinforced. In Experiment 2 (place conditioning with d-amphetamine at 0.0, 1.0, 2.0, 3.3, or 5.0 mg/kg for 3 days), adolescent mice showed no reliable evidence of place conditioning when compared with adults. Hence, 2 main features of adolescence were elevated impulsivity and restlessness, and low (or absent) rewarding efficacy of amphetamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On the respective contributions of awareness of unconditioned stimulus valence and unconditioned stimulus identity in attitude formation through evaluative conditioning.

Evaluative conditioning (EC) is a central mechanism for both classic and current theories of attitude formation. In contrast to Pavlovian conditioning, it is often conceptualized as a form of evaluative learning that occurs without awareness of the conditioned stimulus–unconditioned stimulus (CS-US) contingencies. In the present research, the authors directly address this point by assessing the respective roles of US valence awareness and US identity awareness in attitude formation through EC. Across 4 experiments, EC was assessed with evaluative ratings as well as evaluative priming measures, and the impact of valence and identity awareness on EC was evaluated. EC effects on priming and rating measures occurred only for CSs for which participants could report the associated US valence, and US identity awareness did not further contribute to EC. This finding was obtained both for semantically meaningless (i.e., nonword letter sequences) and meaningful (i.e., consumer products) CSs. These results provide further support for the critical role of contingency awareness in EC, albeit valence awareness, not identity awareness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)