Passive avoidance learning in the rat as functions of d-amphetamine dosage and shock intensity

The effects of d-amphetamine dosage (0, 1, 3, and 5 mg/kg) and shock intensity (0.2, 0.5, and 0.8 ma) on the learning of a passive avoidance response were assessed in rats. A curvilinear dose-response relationship was found at all shock levels, showing slower learning under moderate doses of d-amphetamine. The lowest shock level produced slower learning, especially in conjunction with the lowest dose of d-amphetamine. Results are discussed in terms of freezing behavior.     

The effects of d-amphetamine on temporal discrimination in the rat

The effects of d-amphetamine on temporal discrimination in the rat were studied. Rats were trained on a two-manipulandum task involving the discrimination between two tones differing only in duration. d-Amphetamine (0.1–1.6 mg/kg) disrupted performance on this task, although not in an obvious dose-related manner.Lever biases were enhanced by the drug, but inconsistently among rats. Enhanced lever bias did not necessarily correlate with deterioration of performance. The drug lengthened both response latency and the performance of terminal components of the operant chain. However the characteristic pattern of response latencies produced by the two tones was not altered significantly by the drug.The results are discussed in terms of whether the drug disrupts discrimination performance by a direct effect on processes of temporal discrimination or indirectly, by its other effects on behavior.     

Failure of naloxone to modify the effects of chlorpromazine and d-amphetamine on avoidance behavior in the squirrel monkey

Lever-pressing by squirrel monkeys was maintained under a continuous avoidance schedule in which each response postponed for 30 s the delivery of an electric shock to the tail. Dose-response curves were determined for chlorpromazine (0.03–0.3 mg/kg) and d-amphetamine (0.03–1.0 mg/kg) administered alone and administered concomitantly with 1.0 or 10 mg/kg of aaloxone. The dose-response curves for chlorpromazine and d-amphetamine were similar to those previously reported for monkeys under other schedules of shock-maintained behavior: Chlorpromazine decreased responding in a dose-related manner while d-amphetamine increased responding at low doses and disrupted behavior at the highest dose. Naloxone did not modify the effects of chlorpromazine, and d-amphetamine. These results suggest that interactions observed previously between naloxone and nonopiate drugs on behavior in pigeons and rodents are not general phenomena in all animal species.     

Permanent facilitation of avoidance behavior by d-amphetamine and scopolamine

Scopolamine (0.3, 0.6, 1.2, 2.4, 4.8 mg/kg) or d-amphetamine (0.25, 0.50, 1.00, 2.00, 4.00 mg/kg) was administered daily to independent groups of rats 30 min prior to training in a discriminated, Y-maze avoidance task. A dose-dependent relationship was found between amount of avoidance facilitation and drug dosage. Discontinuation of the drug following asymptotic performance resulted in a decrement in avoidance which varied as a function of the acquisition dosage. Results from a second experiment using the same task indicated that gradually reducing the dosage on consecutive training days rather than abruptly discontinuing the drug was more effective in producing permanent avoidance facilitation in the non-drug condition.     

Effects of d-amphetamine on operant behaviour in the rat

d-Amphetamine given intraperitoneally to albino rats at various doses produced different results, depending on the subjects: it increased the response rate in certain rats while decreasing it in others. These differences depend on the dose as well as on the control response rate. These observations are discussed in the light of possible individual differences at the level of autonomic reactivity.

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Résumé La d-amphétamine injectée I. P. à différentes doses à des rats blancs produit des effects qualitativement différents selon les sujets: chez certains, elle augmente le débit de réponse, chez d'autres, elle le diminue. Ces différences dépendent de la dose et du débit de réponse de contrÔle. Ces conclusions sont discutées à la lumière d'une éventuelle différence individuelle au niveau de la réactivité émotionnelle.

     

Differential effects of methylphenidate and d-amphetamine on stereotyped behavior in the rat

Different equimolar doses of d-amphetamine and methylphenidate were compared for their potency in eliciting stereotyped behavior in rats. Although at lower doses d-amphetamine appeared more effective in causing stereotyped gnawing, repetitive body movements, and sniffing, at higher doses methylphenidate at certain times caused a greater incidence of gnawing than did d-amphetamine. Understanding these differences and comparing related biochemical correlates may lead to a better definition of mechanisms underlying psychostimulant effects.     

Discriminative response control by d-amphetamine and related compounds in the rat

Rats were trained to discriminate between two levers utilizing drug-induced physiological states as discriminative stimuli. Drug injections were associated with reinforcement of response on one lever and saline was associated with reinforcement on the other lever. At equimolar doses, d- and l-amphetamine but not para-hydroxyamphetamine, functioned effectively as cues. Following training, stimulus generalization between these drugs was evaluated. Transfer of response control was observed between the d- and l-isomers, and between para-hydroxyamphetamine and saline in rats trained to utilize d- or l-amphetamine versus saline as cues. These findings suggest the importance of central pharmacological activity in this type of response control.This research was supported by National Institute of Mental Health Grant MH-19651.     

Feeding stimulated by very low doses of d-amphetamine administered systemically or by microinjection into the striatum

The effects of d-amphetamine over a wide range of doses (0.125–4.0 mg/kg IP) on rat unconditioned behaviour were examined in the presence of food and water (experiment 1), in their absence (experiment 2) and after microinjection (2.0 g in 0.5 l) directly into the striatum (experiment 3). In experiment 1 very low doses (0.125 and 0.25 mg/kg) stimulated the intake of food, but not water, and higher doses produced locomotor hyperactivity, rearing, stereotyped sniffing and anorexia. In experiment 2 all doses, including very low doses (0.125 and 0.25 mg/kg), significantly potentiated locomotor activity. In experiment 3, microinjection into the corpus striatum elicited substantial feeding, but not drinking, locomotor activity or stereotyped behaviour. The results suggest that a single graded facilitative mechanism underlies the effects on food intake and other behavioural effects of amphetamine, as implied by a general hypothesis of amphetamine action proposed in the literature, and that these effects may to a large extent by mediated by forebrain dopamine systems.     

The effects of d-amphetamine on the automaintained key pecking of pigeons

Three food-deprived pigeons were initially exposed to an automaintenance procedure in which 8-s response key illuminations were followed by food delivery without regard to the subject's behavior. The percentage of occasions on which key illumination was followed by food delivery was then successively reduced from 100 to 50, 25, 10, and 2.5%. Despite the lack of a programmed contingency between key pecking and food delivery or key illumination, key pecking occurred under all automaintenance conditions. Mean responses per 8-s key illumination during non-drug sessions varied from over 15 to less than one, with the 100 and 50% pairing conditions engendering the highest rates and the 2.5% pairing condition the lowest. Under all automaintenance conditions, d-amphetamine in doses of 0.5, 1, and 2 mg/kg decreased responding in a dose-dependent fashion. Rate-dependent effects were not evident despite the appreciable differences in mean response rates engendered by the various conditions.The senior author is a predoctoral trainee under Psychopharmacology Training Grant USPHS MH-08565, which supported the present research     

Differential effects of chlordiazepoxide and d-amphetamine on responding maintained by a DRL schedule of reinforcement

Rats pressed a lever and obtained food pellets on a schedule of differential reinforcement of low rate (DRL) which required that responses were spaced at least 15 sec apart in order for them to produce reinforcement. When responding had stabilised at slow and steady rates the effects of d-amphetamine and chlordiazepoxide were assessed. Low doses of both drugs increased response rates while higher doses decreased them. Reinforcement frequency showed a dose related decrease after both drugs. When interresponse times (IRTs) were analysed it was found that both drugs shifted the peak of the distribution towards shorter IRTs but that chlordiazepoxide also produced a specific increase in the percentage of responses after very short IRTs (bursts). When IRTs were divided into those following a reinforced response (hit) and those following a non-reinforced response (miss) it was found that bursts normally followed only misses and chlordiazepoxide consistently increased the number of bursts following misses only. Amphetamine did not affect bursts in any consistent way.     

Effect ofPanax ginseng extract on passive avoidance retention in old rats

Female rats of two groups (6 and 27 months) were tested in the passive avoidance test to investigate the age-dependency of the learning ability. The results showed a significantly better avoidance behavior in the young adult animals compared to the older ones. The influence of a 13-day treatment with Panax ginseng (30 mg/kg/d, oral) on 27 month old rats caused a considerably prolonging of the latency time in comparison to the untreated control group of the same age. In the open field the treated rats exhibited neither an altered locomotion nor exploration nor a changed emotional reactivity which could explain the improved avoidance reaction.     

Antagonism of the behavioral effects of cocaine and d-amphetamine by prazosin

Key pecking by pigeons was maintained under a 30-response fixed-ratio schedule of food delivery; lever pressing by squirrel monkeys was maintained under a 3-min fixed-interval schedule of food delivery. Administered alone, d-amphetamine (0.1–3.0 mg/kg), cocaine (1.0–3.0 mg/kg) and bupropion (1.0–30 mg/kg) either did not affect or decreased fixed-ratio responding of pigeons, whereas d-amphetamine (0.056–0.3 mg/kg) either increased or decreased (0.56 mg/kg) responding of monkeys maintained under the fixed-interval schedule. Prazosin, a selective centrally-active alpha₁ antagonist, produced a dose-dependent reversal of the rate-decreasing effects of d-amphetamine and cocaine but not of bupropion on fixed-ratio responding in pigeons. Prazosin also reversed both the rate-increasing and rate-decreasing effects of d-amphetamine on fixed-interval responding of squirrel monkeys. In contrast, the non-selective alpha-antagonist phentolamine enhanced d-amphetamine-induced decreases in fixed-ratio responding. These findings suggest that the behavioral effects of d-amphetamine and cocaine are produced at least in part by activation of central alpha₁ receptors. Prazosin may be a useful tool for better understanding the mechanisms through which cocaine, amphetamine, and other abused stimulant drugs exert their potent behavioral effects.     

Changes in the rate-increasing effects of d-amphetamine and pentobarbital by response consequences

Keypecking in one group of pigeons was maintained under schedules in which food was presented only when a specified number of responses was followed by a 30-s pause without a response. d-Amphetamine and pentobarbital increased low rates of responding (and, thus, decreased food presentation) only after initial injections or when, during drug sessions, responses during the 30-s period did not reset the period. When responses during the pause-interval postponed food delivery, the rate-increasing effects of both drugs diminished over succeeding administrations. Thus, immediate effects of response consequences were as influential as the actual presence of a drug in determining the reproducibility of the behavioral effects of that drug. In a second experiment, keypecking in another group of pigeons was maintained under a 10-min fixed-interval schedule of food presentation but suppressed by a 100-response fixed-ratio schedule of shock delivery (punishment). d-Amphetamine and pentobarbital increased low rates of punished responding when shock delivery was eliminated during drug sessions. Pentobarbital, but not d-amphetamine, also increased punished responding when shock delivery was present. Rate-increasing effects of these drugs were determined by not only predrug patterns of responding but also effects of reinforcers and punishers that occurred during exposure to the drug.     

The effects of d-amphetamine and illumination on behaviors of the squirrel monkey

A behavioral classification and scoring procedure was developed for observing specific responses of squirrel monkeys. The observational procedure along with the photocell method of measuring general activity were then employed to examine the effects of illumination and d-amphetamine on the behavior of squirrel monkeys. It was found that d-amphetamine decreased the incidence of those behaviors seen normally under light conditions while it increased the frequency of behaviours normally seen in the dark.     

Stimulus control and the effects of d-amphetamine in the rat

External discriminative stimuli can modify the behavioral effects of d-amphetamine. Previous work with the pigeon has demonstrated that some aspects of performance on the fixed consecutive number schedule are changed less if a discriminative stimulus indicates when reinforcement is available. This effect has now been replicated with the rat using both simple and multiple schedules. Moderate doses of d-amphetamine (0.56–1.0 mg/kg) usually produced large decreases in reinforced runs when no external cue indicated the possibility of reinforcement. Adding discriminative stimuli when the number requirement was met decreased the drug effect. As was true in the pigeon, response rate measures did not differ between the two stimulus control conditions. Thus, external stimulus control diminishes the drug effect in both species, despite the fact that key pecking was studied in the pigeon and lever pressing in the rat. Evidence was also seen of a possible increase in discriminative stimulus control by d-amphetamine.     

The discriminative stimulus and subjective effects of d-amphetamine in humans

Seventeen normal, healthy adults were trained to discriminate between orally administered d-amphetamine (AMP; 10 mg) and placebo. Standardized subjective effects questionnaires were used to examine the relationship between the subjective and discriminative stimulus effects of AMP. Seven of the subjects were able to learn the discrimination reliably. These seven discriminators did not differ from the ten nondiscriminators in their subjective ratings of mood in the absence of drug. Discriminators were generally more sensitive than nondiscriminators to the subjective effects of AMP, although this difference in sensitivity reached statistical significance only for ratings of hungry. Stimulus substituion was tested in the discriminators with other doses of AMP (2.5 and 5 mg) and with 10 mg diazepam. The discriminative stimulus properties of AMP were dose-dependent, with 5 mg being the threshold dose. In five of the seven subjects the discriminative stimulus properties of diazepam did not substitute for those of AMP. The results demonstrate that the experimental paradigm can be used successfully to study the discriminative stimulus properties of drugs directly in humans.     

Interaction effects of d-amphetamine treatment and ambient temperature on rat's food intake

The thermoregulatory theory of hunger posits that rats placed in a cold environment should increase the amount of food intake, while rats placed in a hot environment should decrease their food intake. d-Amphetamine causes hyperthermia among rats kept at warm ambient temperature, and results in hypothermia among animals kept in a cold environment. d-Amphetamine-caused-hyperthermia should therefore result in decreased eating behavior, and d-amphetamine-caused hypothermia should result in increased eating behavior. One must take into account the fact that d-amphetamine is an anorexic drag. The interaction between (a) ambient temperature, (b) body temperature, and (c) food intake were tested on groups of rats injected with various doses of d-amphetamine (1.5–15 mg/kg) and placed in ambient temperatures ranging from 4–37C. No increase in food intake was revealed under any dosage or temperature condition. The decrease in food intake found with d-amphetamine treated animals could not be explained in the thermoregulatory theory of hunger. Our data indicate that d-amphetamine anorexic effects and thermal effects are mediated by different mechanisms.     

Age-related differences in the effects of d-amphetamine and illumination on fixed-interval responding of rats

The effects of d-amphetamine (0.0, 0.4, and 0.8 mg/kg) on fixed-interval responding in light and dark sensory conditions were examined in rats that were 25, 100, and 200-days-old at the beginning of the experiment. In the youngest and oldest groups, the drug increased responding in light more than in dark. The drug increased responding of the middle age group in the light, but decreased operant rates in the dark. These data appear to support the notion that d-amphetamine reduces the effects of ambient light on behavior in rats.     

Shifting of the d-amphetamine dose-response curve in rats with frontal cortical ablations

Rats trained to bar-press on a FI 15 sec schedule for water reinforcement were administered various doses of d-amphetamine (0.25–4.0 mg/kg) both before and 6–8 weeks after bilateral ablation of frontal cortex. Preoperatively, low doses (e.g. 0.25–0.5 mg/kg) of (d-amphetamine increased responding and high doses (e.g. 2.0–4.0 mg/kg) of d-amphetamine depressed responding. Postoperatively, frontal rats showed larger facilitatory effects in response to low doses of d-amphet-amine but lesser depressant effects in response to high doses of d-amphetamine; the whole dose-response curve was generally shifted higher by the frontal lesions. These results indicate that frontal lesions differentially influence mechanisms mediating two different actions of d-amphetamine.This research was supported by NIMH grant MH21156 and NIMH Research Scientist Development Award (Type 2) DA70082 to S. D. Glick.     

Effects of repeated administration of d-amphetamine on Sidman avoidance responding in rats

The effects of repeated administration of d-amphetamine (0.5 mg/kg SC) on Sidman avoidance responding in rats were investigated. The response (lever-pressing) enhancing effect of d-amphetamine increased progressively after repeated administration. The change in behavior was more marked in the animals exposed to the avoidance situation during the period of the drug effect than in those given the drug after termination of each avoidance session. The present results suggest that the enhancing effect of d-amphetamine as demonstrated on Sidman avoidance responding in rats is dependent on the drug experience of the experimental animals and on the experimental situation to which the animals are exposed during the period of the drug effect.