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At least 1,009 records · Page 56Linked to original sources
PubMed1976

Self-administration of psychomotor stimulant drugs: the effects of unlimited access.

Rhesus monkeys surgically prepared with intravenous catheters were given 23 hr daily access to injection of either cocaine, d-amphetamine, 1-amphetamine, d-methamphetamine or diethylpropion on a fixed ratio 1 schedule of reinforcement for a maximum of 30 days. Responding was maintained by all these drugs but showed both day-to-day and hour-to-hour variability. The two animals self-administering 0.2 mg/kg/infusion cocaine died in less than 5 days. All 6 animals given access to 0.05 mg/kg/infusion d-amphetamine or 0.025 mg/kg/infusion d-methamphetamine also died, but tended to survive more days than animals exposed to cocaine. Three of the 5 animals whose responding was maintained by 0.5 mg/kg/infusion diethylpropion and one of the two animals whose responding was maintained by 0.05 mg/kg/infusion 1-amphetamine survived the entire 30 days despite high rates of intake. Food intake was initially decreased, but often returned to predrug levels and was not related to level of drug intake.

Amphetamine↗
PubMed1977

Effects of diazepam on behaviour suppressed by extinction in pigs.

Diazepam injected to pigs previously trained to perform an operant response for food according to a continuous reinforcement schedule significantly increased resistance to extinction compared to control pigs. In pigs submitted to a time-out procedure diazepam increased the number of nonreinforced responses at the beginning of the acquisition but was unable to disinhibit suppressed behaviour in the later stages of acquisition when the extinguished behaviour was well acquired. The results are discussed with respect to antiaversive or disinhibitory effects of benzodiazepines and an alternative interpretation, the strengthening of the prevailing behavioural tendency in the animal's repertoire at the time of test, is put forward.

Animals↗
PubMed1977

The effects of developmental and/or direct lead exposure on FR behavior in the rat.

In the present study, 21-day old female rats were exposed to daily doeses of 750 mg/kg of lead acetate via restricted water intake regimen for 70-80 days prior to mating. Treatment was then continued throughout gesation and nursing. At weaning, litters from half of the treated and control mothers were placed on treatment for the remainder of the experiment. This manipulation yielded four groups for testing: Group Pb/Pb, developmental and direct, postweaning exposure; Group Pb/C, developmental exposure only; group C/Pb, direct exposure only; and Group C/C, no exposure to lead acetate treatment. Beginning at 42--49 days of age, offspring were shaped to bar press on a Fixed Ratio 20 (FR20) schedule of reinforcement and then received 20 sessions each 20 min in length. Analyses revealed that Group Pb/Pb received significantly fewer reinforcements/min across sessions that the other three groups and also took significantly longer to emit each 20 response block. Contrary to previous reports in the literature, it is suggested that rats may not be impervious to postweaning lead exposure, particularly when there is a history of developmental exposure.

Animals↗
PubMed1978

Tolerance and evidence of physical dependence to daily codeine injections in the rat.

Core temperatures, measured by telemetry, and acquisition of food pellets on a continuous reinforcement schedule were recorded every 30 min in unrestrained male rats given saline for 5 days before and 5 days after 10 daily SC injections of codeine phosphate (200 mg/kg) at 08:00 hr. After the first codeine injection rats were immobile, slightly catatonic, breathed shallowly and had elevated core temperatures, loss of body weight and inhibition of feeding activity. As injections of codeine were repeated, the initial depressant signs decreased and the period of inhibited feeding was replaced by prolonged (greater than 8 hr) post-injection bouts of feeding activity (stimulated feeding) during daylight hours. Core temperatures remained elevated during this phase of drug-induced feeding activity. Mean body weight and 24-hr food intake remained below control levels over the 10-day codeine period as diurnal feeding patterns became reversed. On the first withdrawal day core temperatures declined and feeding patterns changed from those responses on the last codeine day as the rats lost body weight and were hyperirritable. As withdrawal continued core temperature and feeding patterns began to resemble those of the saline control period, body weights increased and hyperirritability subsided. In this study, tolerance and evidence of physical dependence to daily injections of codeine could be demonstrated in rats by continuous monitoring of their diurnal feeding and temperature responses.

Animals↗
PubMed1979

Performance effects with repeated-response measures during pimozide-produced dopamine receptor blockade.

Rats were trained to lever-press for either food reward or brain-stimulation reward on a continuous reinforcement schedule. Following training each animal was extinguished (i.e. tested with the reward omitted) under the influence of pimozide (0.25 mg/Kg or 0.5 mg/Kg). Pimozide produced a dose-dependent reduction in the mean number of responses to extinction made by rats in ecach group. In a second experiment, pimozide produced a similar dose-dependent decrease in the performance of a naturally occurring behavior (nose-poking) that had never been associated with reward. These data suggest that dopamine receptor blockade can produce a perofrmance deficit in situations which require repetitive responses, and that this deficit is unrelated to the presence or absence of reward.

Animals↗
PubMed1979

Effects of acetone and toluene vapors on multiple schedule performance of rats.

Six rats were trained to press a lever for a liquid food reward on a multiple fixed ratio--fixed interval (FR--FI) schedule of reinforcement. When lever-pressing rates became relatively stable, the animals were exposed to 150 ppm of either acetone or toluene for duration times of 1/2, 1, 2 and 4 hr. Exposures were conducted at least three weeks apart. Acetone produced minimal changes on the FR--FI responding during the 1/2 hr exposure. During the 1 hr exposure period, both FR and FI rates increased while during the 2 hr exposure, both FR and FI responses decreased below control levels. During the 4 hr exposure FI responses approximated control levels for 2 rats and were above the control level for the third animal while FR rates were below controls for 2 of the 3 subjects. Rate changes under toluene were generally qualitatively similar to those produced by acetone. An initial enhancement of FR and FI rates occurred during the shorter exposure periods followed by a decrease in rates during the longer exposure periods.

Acetone↗
PubMed1979

Neurochemical basis of the dorsal bundle extinction effect.

Injection of 6-hydroxydopamine into the mesencephalon of the rat has been found to cause resistance to extinction on continuously reinforced schedules. The neurochemical basis of this effect was investigated by using another concentration of 6-hydroxydopamine and by another position of injection. Severe depletion of forebrain noradrenaline was found after these injections with no change in dopamine, serotonin, cholinergic or GABAergic parameters in any brain area measured. The noradrenergic nature of the effect was further shown by the reversal fo the usual behavioural effect following pretreatment with a noradrenaline uptake inhibitor (desimipramine, 25 mg/kg 30 min prior to intracerebral injection of 6-hydroxydopamine). This rules out non-specific damage caused by the 6-hydroxydopamine as the neurochemical basis of the dorsal bundle extinction effect. Failure to find resistance to extinction after either kainic acid or 5-7 dihydroxytryptamine injection seems also to exclude respectively cell body loss at the injection site or damage to serotonergic systems. It is concluded that the dorsal bundle extinction effect is noradrenergic in nature.

5,7-Dihydroxytryptamine↗
PubMed1980

Scopolamine and KCl injections into the caudate nucleus. Overtraining-induced protection against deficits of learning.

To test the hypothesis that extended training of an instrumental task prevents the performance impairments seen after cholinergic and generalized blockade of caudate-putamen complex (NC) activity in animals with a relatively low degree of training, groups of rats were trained to press a lever under a continuous reinforcement schedule for 5, 15 or 25 sessions; The effects of microinjections of scopolamine and potassium chloride into the CN were then assessed. In agreement with early studies in cats, a significant deficit in performance was produced in the animals with a low or medium degree of training, while no changes in learned behavior were seen in the overtained rats. These results show that: (a) normal neural activity of the CN is essential for performance of instrumental behavior during acquisition and early maintenance stages but not after overtraining, and (b) that after extended training the encoding necessary for performance may be transferred to another neural system outside the CN.

Animals↗
PubMed1980

Dorsal periaqueductal gray punishment, septal lesions and the mode of action of minor tranquilizers.

In order to study the role of the septo-hippocampal system and the dorsal periaqueductal gray (DPAG) substance in punished behavior and in the action of minor tranquilizers, two groups of rats were trained to lever press on a continuous reinforcement schedule of food presentation. In one group, every response was subsequently punished by foot-shock delivery; in the other, by brief electrical stimulation of the DPAG of the mesencephalon. In both groups response rats were reduced to less than 10% of pre-punishment rates, but not completely supressed. Response rates did not significantly differ between the two groups, either before or after the introduction of punishment. Septal lesions significantly increased responding in the animals punished by foot-shock, but did not affect responding suppressed by DPAG stimulation. Injection of chlordiazepoxide (5mg/kg,IP) significantly increased punished responding in both groups of rats, before as well as after the septal lesion. Before the septal lesion was made, responding suppressed by foot-shock was significantly more released by chlordiazepoxide than responding punished by DPAG stimulation. These results suggest that in punishment tests using foot-shock, both a behavioral inhibitory system, including the septo-hippocampal structures and an aversive or punishment system, including the DPAG substance, act together to produce response suppression. Both these systems would be depressed by minor tranquilizers in order to cause their anti-punishment and perhaps their anti-anxiety action as well.

Animals↗
PubMed1981

Effects of narcotic abstinence on schedule-controlled behavior in dependent rats.

Female Sprague-Dawley rats were trained to lever press for food on a variable interval one minute schedule of reinforcement. Four of these rats were then made tolerant to and physically dependent on morphine by a series of automatic IV injections. Four other rats were made tolerant to and physically dependent on LAAM. During the dependence state behavioral tolerance was exhibited to the suppressant effect of morphine on lever pressing, but not to the suppressant effect of LAAM. Abstinence was induced by discontinuation of injections. During both the morphine and LAAM abstinence states from the fourth through twelfth days mean lever presses per session were significantly higher than pre-drug control values. However, there were quantitative differences. Mean lever presses per session were significantly higher during morphine abstinence than during LAAM abstinence. This difference in degree of increased lever pressing observed during morphine and LAAM abstinence in this study extends our previous reports which demonstrated that in the rat morphine abstinence was associated with more severe behavioral disruptions than LAAM abstinence.

Animals↗
PubMed1983

Drug dependence: myth or motive?

The acceptability of nonmedical use for a particular drug is a function of diverse social needs. Drug dependence is due less to intrinsic effects than to the situation in which drug taking occurs. An addictive level of drug self-administration is a symptom of behavioral troubles rather than a definition of the trouble itself. The intrinsic effects of drugs do not in themselves produce either misuse or evoke specific kinds of behavior such as sexual or aggressive activities. Drugs can, however, come to function as discriminative stimuli for socially sanctioned behavior that would not under other circumstances be tolerated. The intrinsic reinforcing potential of an agent evolves in and dominates situations in which other reinforcing opportunities are either absent or remain unavailable to an individual who is unprepared to exploit them. While certain intrinsic properties of a drug contribute to its potential as a reinforcer (e.g., rapid onset and brief duration of action), reinforcing efficacy is notoriously malleable. It is a function of historic and currently-acting factors, particularly social reinforcers. The importance of physical dependence in the maintenance of drug seeking and taking is mainly unproven and probably overrated. Situations under which important reinforcers are available only in small portions intermittently can induce various excessive activities, including an untoward concern with obtaining and using drugs. Drug dependence prevention as a species of environmental dependence can be best effected by either alterations in the intermittent reinforcement situations inducing excessive behavior or by providing opportunities and training with respect to reinforcing alternatives other than drugs.

Aggression↗
PubMed1983

Interrelationships between behavior and pharmacology as factors determining the effects of nicotine.

Behavioral consequences play an important role in determining subsequent behavior. The specific effects a particular consequent event will have, however, depend on many factors. Under certain conditions, the same event can produce diametrically opposite effects on behavior. Nicotine and electric shock are events which can function either as reinforcers capable of maintaining behavior, or as punishers which can suppress behavior. The reinforcing or punishing properties of consequent events depend on the prior experience of the organism and on the conditions existing at the time those events occur. The study of these pivotal events, and of those factors which contribute to their dual behavioral effects, has provided important information for developing a better understanding of general processes governing behavior. Further, the results of these studies have clarified the role of both behavioral and environmental factors in the initiation and maintenance of drug-taking behavior.

Animals↗
PubMed1984

Stimulus control by diazepam of behavior maintained under fixed-ratio stimulus-shock termination schedules in rats.

The stimulus control of behavior by diazepam (1.0 mg/kg) was investigated where responding was maintained under fixed-ratio (FR) schedules of stimulus-shock termination in rats. The size of the FR requirement was either 1, 5, 10, or 20 responses. At each FR requirement, dose-effect curves were determined for diazepam, flurazepam, pentobarbital and cyproheptadine. Diazepam-like discriminative stimuli were produced by flurazepam and pentobarbital but not by cyproheptadine. The magnitude of the FR requirement had no significant effect on the dose-effect curves for percentage of responses emitted on the diazepam-appropriate choice lever for any of the four drugs. On the other hand, the effects of these drugs on rates of responding depended on the magnitude of the FR requirement. None of the drugs altered response rates under the FR1 schedule. Diazepam tended to increase response rates under the FR5 schedule, but had no effect or decreased rates under the FR10 and FR20 schedules. Flurazepam and pentobarbital predominantly decreased rates at FR requirements of 5, 10 or 20 responses. Cyproheptadine had no significant effect on response rates at any schedule parameter. Together with previous reports, the present results indicate that the discriminative effects of diazepam are similar under schedules employing noxious (this study) or non-noxious (other reports) consequences, even though the effects on response rates of diazepam-like drugs differ depending on the schedule of reinforcement and consequent event maintaining the behavior.

Animals↗
PubMed1985

Effects of caffeine and L-PIA on rats with selective damage of the hippocampal system.

Rats with electrolytic lesions of either the medial septum or hippocampus or with colchicine-induced lesions of the dentate granule cells produced significantly higher amounts of lever pressing as compared to controls on both V150 sec and VT50 sec reinforcement schedules. Caffeine, at doses of 3.2, 10, and 32 mg/kg, produced a dose-related decrease in operant responding for all lesioned animals while having little effect on the responding of controls. L-PIA (an adenosine analog), at doses of 0.01, 0.05, and 0.10 mg/kg, produced similar but more variable effects in some of the groups tested and did not alter the rate-reducing effects of caffeine (32 mg/kg) when given concurrently (0.05 mg/kg). Caffeine administration also appeared to coincide with a long-term decrease in response rates that continued after cessation of its administration. Explanations are advanced as to caffeine's possible mode of action in this experiment. The postulate that colchicine-induced damage of dentate granule cells might be a viable animal model of some forms of hyperactivity also is advanced. This specific lesioning procedure, by itself, produced animals which displayed significantly higher than normal levels of general activity which were also sensitive to caffeine's rate-decreasing effects.

Adenosine↗
PubMed1985

Effects of opioid antagonists and their quaternary derivatives on locomotor activity and fixed ratio responding for brain self-stimulation in rats.

Rats were implanted with stimulating electrodes aimed at the midbrain-central gray area (MID-CG) and trained to lever press for brain stimulation (ICSS) on a fixed ratio:30 (FR:30) schedule of reinforcement. When response rates were stable, animals were administered either naloxone hydrochloride, naltrexone hydrochloride, naloxone methobromide or naltrexone methobromide in a dose range of 0.1-30 mg/kg. Fifteen minutes after the subcutaneous administration of either drug or vehicle, animals were tested for 45 min in the ICSS procedure and changes in response rates following drug administration were compared with those following vehicle administration. Both naloxone and naltrexone hydrochloride produced graded decreases in responding over the entire dose range, while naloxone and naltrexone methobromide did not alter response rates at any dose level. In a separate testing procedure, 30 mg/kg naloxone and naltrexone hydrochloride produced modest reductions in motor activity, while the methobromide derivatives did not. These results demonstrated that the fixed ratio procedure was sensitive to changes in responding for ICSS produced by opioid antagonists, and this effect depends upon the entry of these opioid antagonists into the brain.

Animals↗
PubMed1985

Effects of quipazine and of tryptamine on self-stimulation of median raphé nucleus and of lateral hypothalamus in rats.

Separate groups of male Wistar rats were trained to lever press on a continuous reinforcement schedule under which behaviour was maintained by electrical stimulation of the median raphé nucleus (N = 6) or the lateral hypothalamus (N = 6). The effects of several doses of quipazine (2.5-7.1 mg/kg) and of tryptamine (10-80 mg/kg) were assessed with each group. Administration of quipazine resulted in a decrease of median raphé self-stimulation at 5.0 and 7.1 mg/kg. This compound had no statistically significant effect on lateral hypothalamic self-stimulation. Administration of tryptamine resulted in significant decreases in self-stimulation at both sites, however, whereas the effects of this drug were significant at 20, 40 and 80 mg/kg with median raphé self-stimulation, a significant decrease in lateral hypothalamic self-stimulation was only observed at 80 mg/kg. As baseline response rates differed in the two self-stimulation sites, a second group of animals with lateral hypothalamic sites (n = 6) were tested with quipazine (2.5-7.1 mg/kg) at an overall baseline response rate matched to that of the median raphé group. Although a tendency to decrease self-stimulation rates was found in this group, these results were not significant. These data suggest, therefore, that median raphé self-stimulation is more sensitive than lateral hypothalamic self stimulation to disruption by the effects of quipazine and tryptamine.

Animals↗
PubMed1985

Asymmetrical effect of unilateral cortical lesions and amphetamine on DRL-20: a time-loss analysis.

Male Sprague Dawley rats received unilateral 1.5 mm diameter focal suction lesions of either the left or right orbito-frontal cortex and were tested for response to 6 doses of amphetamine sulfate ranging from 0.5 to 1.5 mg/kg on a DRL-20 schedule of reinforcement. Right hemispheric lesion animals obtained a greater number of control reinforcements and were more sensitive to amphetamine's disruptive effects, showing a greater dose-related decrease in water rewards obtained than left lesion animals. An analysis method is introduced which combines the interactive effects of premature responses and their IRT value in a way that relates directly to reinforcement attainment. Calculated total session time made unavailable for reinforcement due to premature responding, correlated negatively (r = -.942) with the number of reinforcements obtained.

Amphetamine↗