Modification of the behavioural effects of amphetamine by a GABA agonist in a primate species

Abstract

Acute administration of d-amphetamine in the marmoset results in a dose dependent increase in small head movements (checking), and an almost total suppression of purposeful activities and social interaction. It has little effect on locomotion and does not induce stereotyped gnawing. The GABA-agonist, muscimol, decreases checking, locomotion, activities and social interaction when given alone, but induces jerking movements at large doses. When administered in combination with amphetamine, muscimol induces persistent stereotyped gnawing. On the basis of the present findings and those of experiments in rodents it is suggested that compulsive gnawing results from overactivity in the striatal efferent pathway, while checking is probably mediated by extra-striatal sites. Since the behavioural effects of muscimol resemble those of the typical neuroleptics with the exception of the induction of gnawing, it is suggested that muscimol, though sedative, may counteract certain extrapyramidal effects of neuroleptic treatment while facilitating their other behavioural effects.

Stereotyped responding by schizophrenic patients on a two-choice guessing task

“…Ridley et al 1979;Robbins, 1982). This is clearly because most of the symptoms of schizophrenia cannot be observed in animals, because they either involve language (thought disorder, poverty of speech) or are accessible only by subjective experience (delusions, hallucinations).…”

Phencyclidine-induced increases in striatal neuron firing in behaving rats: reversal by haloperidol and clozapine

“…When administered to animals, these drugs elicit a pattern of repetitive behavior (stereotypy), which requires an intact dopaminergic projection to the striatum and other forebrain sites (Dunnett and Robbins, 1992;Rebec and Bashore, 1984). In fact, amphetamine not only releases striatal dopamine (Butcher et al, 1988;Kuczenski and Segal, 1989;Zetterstr6m et al, 1983), but the behavioral effects of this drug are blocked either by neuroleptics (e.g., Megens et al, 1992;Moore and Kenyon, 1994;Ridley et al, 1979;Rollema et al, 1976;Tschanz and Rebec, 1988), which block dopamine receptors (Ellenbroek, 1993;Reynolds, 1994;Seeman, 1980), or by destruction of dopaminergic terminals in the striatum (Creese and Iversen, 1975;Fibiger et al, 1973;Fink and Smith, 1980;Kelly et al, 1975). Thus, stria.tal dopamine has been linked not only to the behavioral effects of amphetamine but also to idiopathic schizophrenia (Carlsson, 1978;Laduron, 1989;Seeman and Van Tol, 1994).…”

An investigation of the effects of intracerebral injection in the marmoset of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease

“…The group to which each animal belonged could not be recognized from qualitative assessment of its behaviour. Although there is a resemblance between amphetamine psychosis and schizophrenia (Connell, 1958), group III animals did not develop either increased 'checking' as seen after acute amphetamine treatment or the excessive self-grooming and decreased locomotion induced by chronic amphetamine administration (Scraggs & Ridley, 1978;Ridley et al 1979). Nevertheless, certain differences between the groups which are both statistically significant and sustained have become apparent, and these differences are confirmed by automatic measurements with an activity monitor which precludes observer bias.…”

“…Before operation each animal was subjected to simple neurological tests (responses to sensory stimulation, muscle tone and motor coordination) and its behaviour in the home cage was assessed serially and quantitatively with a microprocessor. This technique is a sensitive measure of the effects of a variety of drugs (Ridley et al 1979).…”