The effect of intracerebral administraton of antagonists of dopamine and noradrenaline upon the locomotor stimulation induced by intraperitoneal injection of d-amphetamine sulfate in rats was investigated. Inj ection of low doses of the dopamine antagonist haloperidol (2.5 mug and 5 mug) bilaterally into the nucleus accumbens antagonized the locomotor stimulation following d-amphetamine. No significant inhibition was observed following administration of the alpha-adrenergic antagonist phentolamine or thhe beta-adrenergic antagonist propranolol into the nucleus accumbens. Injection of the dame doses of haloperidol into the caudate nucleus did not inhibit the d-amphetamine induced locomotor activity in contrast to the effects seen following injection into the nucleus accumbens. The results confirm the significance of dopaminergic mechanisms for the locomotor stimulant effect of d-amphetamine and indicate that the mesolimbic dopamine system plays an important role in this respect.
The effects of injections of monoamines, alone and in combination with different antagonists, bilaterally into the nucleus accumbens of nialamide-pretreated rats were investigated. Dopamine was found to produce a stronger stimulation of locomotor activity than noradrenaline, whereas serotonin was effective only in a small number of animals, in which the duration of locomotor stimulation was shorter than after dopamine or noradrenaline. The effects of both dopamine and noradrenaline were completely antagonized by administration of a small dose of the dopamine antagonist haloperidol, administered bilaterally 15 min after the catecholamines. The alpha-adrenergic antagonist phentolamine did not inhibit the effect of noradrenaline but, on the contrary potentiated and considerably prolonged the duration of locomotor stimulation. Aslo, the effect of dopamine was potentiated and prolonged by phentolamine. Bilateral injection of phentolamine alone had no influence upon locomotor activity. The effect of noradrenaline was not clearly inhibited nor potentiated by the beta-adrenergic antagonist propranolol. It is suggested that the stimulation of locomotor activity induced by injection of noradrenaline into the uncleus accumbens of nialamide-pretreated rats is brought about via dopaminergic mechanisms.
The effect of micro-injections of dexamphetamine chloride into the neostriatum, the nucleus accumbens, the anterior hypothalamus, and the ventricular system on self-stimulation with electrodes in the ventral tegmentum was studied. Unilateral injections of 10 mug into the anterior hypothalamus produced no effect. Injections into the neostriatum tended to depress the self-stimulation rate, whereas injections into the nucleus accumbens increased the rate markedly. Bilateral injections (2 times 2.5 mug and 2 times 5 mug amph.) into the nucleus accumbens were more effective than unilateral injections and were as effective as systemic injections of 1 mg/kg amphetamine (i.p.). Bilateral injections into the neostriatum also increased the self-stimulation rate. Injections of 10 mug into the ventricular system resulted in a smaller increase which was not statistically significant. These results are discussed in relation to the involvement of the dopaminergic system in the maintenance of self-stimulation behaviour.
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