Acute Effects Of D-amphetamine Research Articles

Oral d-amphetamine increases sensitivity to negative consequences on an associative learning task in cocaine users

Oral d-amphetamine increases sensitivity to negative consequences on an associative learning task in cocaine users

The acute effects of d-amphetamine and d-methamphetamine on ERP components in humans

While a number of behavioural studies have been conducted to investigate the acute effects of amphetamines on tasks of attention and information processing, there is currently a scarcity of research concerning their electrophysiological effects in healthy adults. It is also unclear as to whether amphetamines exert effects on stimulus evaluation or response selection. In two studies, independent groups of twenty healthy illicit stimulant users aged between 21 and 32years were administered 0.42mg/kg d-amphetamine versus placebo, and 0.42mg/kg d-methamphetamine versus placebo respectively, and completed an auditory oddball task on two separate testing days. A 62-channel EEG was recorded during the completion of the task, and the effects of amphetamines on N200 and P300 ERP components were analysed. d-amphetamine significantly decreased reaction time, improved accuracy, and reduced the latency of the P300 component relative to placebo, while having no effect on the N200 component. d-methamphetamine had no effect on reaction time, accuracy or the P300 component, but reduced the amplitude of the N200 component, relative to placebo. It was concluded that there is tentative support to suggest that d-amphetamine at a dose of 0.42mg/kg may enhance speed of information processing while d-methamphetamine at a dose of 0.42mg/kg may reflect changes to stimulus evaluation.

The acute effects of d-amphetamine and methamphetamine on attention and psychomotor performance

It is not clear how the deleterious effects of amphetamines on driving performance are mediated in terms of select cognitive processes. The current three separate experiments assessed the acute effects of an oral dose of either 0.42-mg/kg d-amphetamine, d,l-methamphetamine and d-methamphetamine on driving-related cognitive functions in a total of 60 healthy non-fatigued adults. Three separate repeated measures counterbalanced, double-blind, placebo-controlled designs were employed in which 20 volunteers completed two treatment conditions, either d-amphetamine, d,l-methamphetamine or d-methamphetamine and placebo. Performance was assessed on a range of attentional, psychomotor and perceptual speed tasks. Mean blood concentrations at 120-, 170- and 240-min postdrug administration were 83, 98 and 96 ng/ml, respectively, for d-amphetamine, 90, 95 and 105 ng/ml, respectively, for d,l-methamphetamine and 72, 67 and 59 ng/ml, respectively, for d-methamphetamine. The amphetamines, in general, improved various aspects of attention (Digit Vigilance, Digit Symbol Substitution Test and Movement Estimation Performance) with some evidence to suggest possible enhancement in psychomotor functioning (Tracking ability) and perceptual speed (Inspection Time). The current series of studies primarily provides evidence of low-level amphetamine-related enhancement of function; however, it also provides evidence of less conservative movement estimation that might contribute to amphetamine-related road fatalities.

Effects of acute D-amphetamine and ketamine on the performance of rats in a serial negative patterning procedure.

This study assessed the effects of acute amphetamine and ketamine on the performance of rats in a serial negative patterning procedure. A 5 s auditory target stimulus and a 5 s visual feature cue were each followed by food, but the target stimulus was not followed by food if preceded by the feature. There was a 5 s empty gap between feature termination and target onset in the latter, non-reinforced trials. Thus, the feature functioned as a cue signalling the non-reinforcement of the target. The interval between the feature and the target was varied in the non-reinforced trials following pretreatment with subcutaneous saline, D-amphetamine (0.5 mg/kg) or ketamine (5 mg/kg). The main behaviour measured was visits to the place of food delivery during target presentation. Under saline, the response frequency during the target was lowest when the interval between the feature and the target exactly matched the interval used during training. Either shortening or lengthening the interval enhanced responding. Neither D-amphetamine nor ketamine disturbed this temporal pattern, although D-amphetamine and ketamine non-specifically increased and decreased response frequencies, respectively, in all the trial types. The results are discussed in the framework of the amphetamine and ketamine models of schizophrenia.

Acute Effects of d-Amphetamine During the Early and Late Follicular Phases of the Menstrual Cycle in Women

Recent preclinical evidence indicates that ovarian hormones, such as estrogen and progesterone, may influence the behavioral effects of psychoactive drugs by interacting directly with neurotransmitter systems in the central nervous system. However, few studies have examined the effects of ovarian hormones on subjective or behavioral responses to psychoactive drugs in humans. In the present study, we assessed the subjective and physiological effects of d-amphetamine during the early and late follicular phases of the menstrual cycle. Nineteen healthy, regularly-cycling women participated in four sessions receiving doses of d-amphetamine (AMPH; 15 mg oral) or placebo during the early and late follicular phases of two menstrual cycles. During the early follicular phase levels of both estrogen and progesterone are low, whereas during the late follicular phase estrogen levels are higher while progesterone remains low. Dependent measures included self-report questionnaires, physiological measures and plasma hormone levels. Most of the subjective and physiological effects of AMPH were not affected by menstrual cycle phase. However, subjects reported greater Unpleasant Stimulation after AMPH, and less Unpleasant Sedation, during the late follicular phase than during the early follicular phase. These results provide limited evidence that higher levels of estrogen during the late follicular phase alter the subjective effects of AMPH in normal, healthy women.

Effect of conditioning with d-amphetamine on the extracellular concentration of dopamine and its metabolites in the striatum of behaving rats.

The effect of classical conditioning with d-amphetamine on the extracellular concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of awake, freely moving rats was studied using microdialysis. This was done in order to test, whether there occurred alterations in DA release as conditioned responses in the striatum. The first series of experiments studied the acute effects of d-amphetamine on the concentration of DA and its metabolites DOPAC and HVA. d-Amphetamine (2 mg/kg, s.c.) increased extracellular DA and decreased DOPAC and HVA. Behaviorally, it led to stereotyped locomotor activation and sniffing. In principle, these observations confirmed earlier findings. In a second series, conditioned responses to d-amphetamine were studied. Rats were implanted with guide cannulas prior conditioning experiments started. For conditioning experiments, the rats were divided into three groups: conditioned group, pseudoconditioned group and a drug-naive control group. After 7 daily training sessions with d-amphetamine (2 mg/kg), on the 8th day, the test day, rats were injected with saline and exposed to the conditional stimuli, while they were observed for their stereotyped, conditioned response. Additionally, microdialysis was performed in order to observe possible changes in the extracellular transmitter or metabolite concentrations. Conditioning with amphetamine led to conditioned stereotypic behavior. In comparison with the pseudoconditioned rats, there was an increase in DA release as conditioned response to amphetamine. In pseudoconditioned rats. DOPAC and HVA were slightly higher than in both other groups. DOPAC and HVA were lower in rats conditioned to d-amphetamine when compared with the pseudoconditioned ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Behaviour in the novel environment predicts responsiveness to d-amphetamine in the rat

The behaviour of rats in a novel environment was studied using a rapid time-sampling observation procedure followed by a principal component analysis (PCA) of the data. This approach revealed that novel environment behaviour can be described by two factors or principal components. The first factor comprised rearing, sniffing-up, ambulation and locomotion (photocell counts), and was termed "Escape". The second factor, which had high positive loadings of sniffing-down and locomotion and a high negative loading of immobility, was termed "Exploration". The scores of individual rats on the "Escape" factor predicted the stimulatory effect of acutely administered d-amphetamine (1.5mg/kg) on unconditioned behaviour. "Escape" high responders (HRs) showed more behavioural stimulation than "Escape" low responders (LRs). However, the locomotor stimulatory response of both groups increased after long-term, periodic administration of d-amphetamine and drug discrimination training, such that the level of drug-induced locomotor activity was now equivalent for the two groups. The same rats were tested twice with various doses of d-amphetamine after being trained to discriminate this drug (0.5mg/kg) from saline. "Escape" HRs were less sensitive than "Escape" LRs to the discriminative effects of 0.125-0.25mg/kg d-amphetamine. In contrast to these findings, "Exploration" HRs and LRs were not different on any of the dependent measures described above. These results are discussed in relation to the possibility that "Escape" factor scores are an indication of an animal's responsivity to novelty-induced stress. If this is the case, then animals which are more susceptible to the effects of novelty stress are more sensitive to the locomotor stimulating effects of acute d-amphetamine, but less sensitive to the cueing properties of low doses of this drug.

Acute effects of d-amphetamine in a monkey operant behavioral test battery

The acute effects of d-amphetamine were assessed using a battery of complex food-reinforced operant tasks that included responding in delayed matching-to-sample (DMTS, n=6), conditioned position responding (CPR, n=7), progressive ratio (PR, n=8), temporal response differentiation (TRD, n=4), and incremental repeated acquisition (IRA, n=9) tasks. Performance in these tasks is thought to depend upon specific brain functions such as short-term memory and attention (DMTS), color and position discrimination (CPR), motivation to work for food (PR), time perception (TRD), and learning (IRA). d-Amphetamine sulfate (0.01–1.0 mg/kg IV), given 15-min presession produced significant dose-dependent decreases in the number of reinforcers obtained in each task. Response accuracy was significantly decreased at doses of 0.3 and 1.0 mg/kg for TRD and at 1.0 mg/kg for CPR when compared to saline injections. Accuracy was not consistently affected in the DMTS or IRA tasks. Response rates decreased or response latencies increased significantly at doses of 0.3 and 1.0 mg/kg in the PR and DMTS tasks. A dose of 0.1 mg/kg for the IRA and TRD tasks, 0.3 mg/kg for DMTS and 1.0 mg/kg for the CPR tasks significantly decreased percent task completed. Thus, the relative sensitivities of these tasks for detecting d-amphetamine behavioral effects were IRA = TRD > PR = DMTS > CPR. These results indicate that in monkeys, performance of operant tasks designed to model learning ability and time perception is more sensitive to the disruptive effects of d-amphetamine than is performance in tasks designed to model motivation, short-term memory and attention, which is more sensitive than tasks that model color and position discrimination.

Incremental repeated acquisition in the rat: Acute effects of drugs

Rats lever pressed for food and learned new response sequences on three levers. At the beginning of each daily session, responses on only one of the levers produced food. After meeting criterion on one lever, the task was "incremented" so that sequential responses on two levers were required and so on up to five sequential responses. Each new required response was added in front of the previously performed sequence. Sequences of lever presses required to produce food changed each session. Following establishment of stable acquisition behavior, the acute effects of d-amphetamine (0.30-3.0 mg/kg), diazepam (0.125-4.0 mg/kg), morphine (0.30-10.0 mg/kg), pentobarbital (1.0-17.5 mg/kg), and chlorpromazine (0.10-3.0 mg/kg) were examined. All drugs decreased the number of response sequences completed in a dose-dependent fashion. Response rates generally decreased at or below those doses that caused an increase in errors. For d-amphetamine, the profound disruption of incremental repeated acquisition behavior was primarily due to drug-induced perserverative responding. Pentobarbital and chlorpromazine increased errors both when the sequence was incremented and within the sequence whereas diazepam only increased errors when the sequence was incremented. Morphine generally increased within sequence errors without affecting errors when the sequence was incremented.

Alteration of response patterning by d-amphetamine on repeated acquisition in rats

The acute effects of d-amphetamine on response patterning in a repeated acquisition baseline were investigated with rats. Each session the animals acquired a different four-member response sequence on three levels. Each sequence (trial) completion produced a food pellet. Errors produced a brief timeout that was reset by responses made during the timeout. Acute doses of d-amphetamine (0.5–4.0 mg/kg) and saline were administered 30 min presession. The response patterns analyzed were perseverative responses to a single lever (runs), and a response to each lever in either a left-to-right or right-to-left direction (tranerses). The trial position, frequency, and lever location of error and timeout responses that occurred in the context of runs and traverses were studied. In contrast to control sessions, higher doses of d-amphetamine produced increases in the number of error and timeout responses emitted. The majority of these responses occurred as runs; traverse responding did not exceed control levels. Furthermore, the run error and timeout responding tended to occur early in the session and on a siingle response lever. The results are consistent with the view that d-amphetamine disrupts stimulus control and produces perseverative responding which may account for previous reports of disruption in repeated acquisition tasks following d-amphetamine administration.

Effects of d-amphetamine and cocaine on repeated acquisition with timeout from avoidance

The acute effects of d-amphetamine and cocaine on a repeated acquisition baseline with timeout from avoidance were investigated in two rats. Each session the animals acquired one of two different three-member response sequences. Each sequence member was associated with a different response lever. The first two correct responses of each sequence postponed shock for a fixed period of time. The third correct response initiated a signalled timeout (30 sec) from avoidance. Incorrect responses did not postpone shock. The baseline performance was characterized by a decrease in errors within each session, similar to patterns of repeated acquisition maintained by food. In comparison to control sessions, both d-amphetamine and cocaine increased errors and altered the pattern of within-session acquisition. d-Amphetamine increased the rate of sequence completion and the rate of shock delivery in both animals. Cocaine increased the rate of sequence completion in one animal and increased the rate of shock delivery for the other.