Showing papers by "Trevor W. Robbins published in 1983"

Contrasting interactions of pipradrol, d-amphetamine, cocaine, cocaine analogues, apomorphine and other drugs with conditioned reinforcement.

Abstract: The effects of various psychomotor stimulant drugs and drugs outside this class were examined on the efficacy of stimuli previously paired with reinforcement or reward (conditioned reinforcers, CR) in controlling responding. Pipradrol (5-45 mumol/kg), d-amphetamine (1.25-15.0 mumol/kg), and the cocaine analogues WIN 35,428 (0.1-30.0 mumol/kg) and in one of two determinations WIN 35,065-2 (0.1-29.0 mumol/kg) all generally increased responding on a lever providing CR, but did not change or decreased responding on a lever providing no CR (NCR). Cocaine (5-125 mumol/kg) and chlordiazepoxide (3.75-60.0 mumol/kg) had no significant effects. Morphine (3.2-32.0 mumol/kg) and alpha-flupenthixol (0.02-2.0 mumol/kg) generally reduced responding on both levers. Apomorphine (0.1-1.0 mumol/kg) generally increased responding on both levers. Neurochemical data showed that d-amphetamine was generally more potent than pipradrol in its effects on in vitro monoamine uptake and release.

Increased response switching, perseveration and perseverative switching following d-amphetamine in the rat.

Abstract: Four experiments examined the effects of d-amphetamine on response switching and perseveration in apparatus allowing a choice of response location. The relative ‘cost’ of a switch between two response locations and repetitive responding at a single location by rats was manipulated in the various test settings to provide baseline probabilities of switching. d-Amphetamine (0.2–2.3 mg/kg) increased response switching. This effect did not depend on switching being necessary to produce reinforcement and was not explained by increases in locomotor activity, motivational change or randomisation of responding. Further evidence was provided in support of a ‘probability-dependency’ hypothesis, that the effect of the drug depends in part upon the baseline probability of a response. A measure of perseveration independent of response switching (extra responses made prior to the collection of food) showed that increased switching and increased perseveration occurred in the same situation at the same doses, although perseveration generally occurred at higher doses than increased switching. Therefore the effect of amphetamine on response switching or repetition depends on the dose of drug, the context of the response and its probability of occurrence under control conditions.

Effects of d-amphetamine and apomorphine upon operant behavior and schedule-induced licking in rats with 6-hydroxydopamine-induced lesions of the nucleus accumbens.

Abstract: After training under a fixed-interval 60 sec schedule of food presentation in the presence of a water tube (to permit schedule-induced licking), groups of rats received either 6-hydroxy-dopamine (6-OHDA)(8 micrograms base/2 microliters) or 0.2% ascorbate-0.9% saline vehicle bilaterally into the nucleus accumbens. 6-OHDA produced greater than 80% depletion of the catecholamines dopamine and norepinephrine and the dopamine metabolite dihydroxyphenylacetic acid in the nucleus accumbens and olfactory tubercle, but nonsignificant depletions in the corpus striatum. The behavior of the groups treated with 6-OHDA ("lesion") and vehicle ("sham") was assessed for up to 58 days postoperatively. In the first few days after 6-OHDA, the lesion group showed reductions in high rates of responding toward the end and in high rates of licking at the beginning of the fixed-interval. However, licking was increased during later portions of the fixed interval in the lesion group. d-Amphetamine (0.25-2.0 mg/kg) increased low rates but decreased high rates of schedule-controlled responding, while generally reducing licking. The lesion group showed attenuated rate-reducing effects of d-amphetamine. In contrast, the lesion group showed enhanced rate-reducing effects of apomorphine (0.025-0.1 mg/kg) on both schedule-controlled responding and schedule-induced licking. In a second determination of the effect of d-amphetamine (0.25-2.0 mg/kg), schedule-induced locomotor activity was recorded and the water tube was removed. The lesion group showed attenuated rate-increasing and rate-decreasing effects of d-amphetamine upon schedule-controlled responding and reductions in the drug-induced increases in locomotor activity. The results are discussed in terms of the functions of dopamine in the control of behavior and in the mediation of the response to d-amphetamine and apomorphine.

Dissociable effects of d-amphetamine, chlordiazepoxide and α-flupenthixol on choice and rate measures of reinforcement in the rat

Abstract: The role of reinforcers in influencing choice was studied by use of a schedule that included a random intermixing of reinforced and explicitly non-reinforced components The just-reinforced response had a high likelihood of being repeated (win-stay), although there was no differential reinforcement for doing so, whereas responses just followed by explicit non-reinforcement had a very low probability of repetition (lose-stay) Non-parametric indices based on the theory of signal detection were used to derive a choice measure of reinforcement which was independent of alterations in average response rate Treatments with d-amphetamine (02–45 mg/kg), chlordiazepoxide (025–16 mg/kg) and α-flupenthixol (003–06 mg/kg) showed that changes in the choice measure could be dissociated from changes in the response rate These findings were supported by extinction and satiation tests

Behavioral and pharmacological specificity of the feeding elicited by cholinergic stimulation of the substantia nigra in the rat.

Abstract: Microinjections of the cholinergic agonist carbachol into anterior substantia nigra dose dependently increased food intake in satiated rats. This resulted from a prolongation of the duration of eating. In the absence of food, those doses of carbachol that stimulated food intake (.1 and .5 microgram) had no effect on any other response examined, including gnawing, drinking, locomotion, grooming, sniffing, and rearing. The effect of carbachol depended on the degree of prior food deprivation, but supra-additive effects of carbachol and deprivation were not observed. These results are contrasted with those of previous studies demonstrating the nonspecific behavioral effects of electrical stimulation of the brain and of studies showing that carbachol has radically different behavioral effects at other central nervous system sites. Microinjection of an acetylcholine/eserine sulfate mixture also significantly increased food intake. This response was abolished by prior microinjection of the muscarinic receptor antagonist atropine into the substantia nigra, a result that provides evidence for pharmacological specificity of the behavioral effects. These data provide further evidence for the hypothesis that a functional cholinergic system is present within substantia nigra.