Noradrenergic and cholinergic action on neuronal activity during self-stimulation behavior in the rat

Abstract

The effects of drugs with adrenergic and cholinergic actions were studied in unanaesthetized, freely behaving rats. Pairs of drugs—of which the first in each pair suppressed responding and the second one reinstated it—were tested in rats during self-stimulation behavior while effects on neuronal activity correlated with this behavior were determined. Two types of neuronal responses were studied. The first was the occurrence of spikes with fixed latencies in relation to stimulation applied in the posterior lateral hypothalamus. The second was the suppression of spontaneously active neurons as a function of stimulation in the posterior lateral hypothalamus. The first type of response was studied in the cingulate, the preoptic and the ventral midbrain regions. The second type was studied in the middle hypothalamus. The drugs with adrenergic action were tetrabenazine and (+)-amphetamine; the drugs with cholinergic action were physostigmine and scopolamine. The second drug in each pair was administered 30 min after the first one and at the time of maximal effect of the first drug on self-stimulation behavior. Tetrabenazine reduced spike activity with fixed latencies in the ventral midbrain region, but not in the cingulate and the preoptic regions at the time when it suppressed self-stimulating behavior. Amphetamine partially restored the frequency of spikes with fixed latencies in the midbrain region at the time when it reinstated self-stimulation behavior. Tetrabenazine reduced the suppressant effect of stimulation in the posterior hypothalamus (disinhibition) on neuronal activity in the middle hypothalamus. Amphetamine reinstated partially the suppressant action of stimulation on neuronal activity recorded in the middle hypothalamus at the time it reinstated self-stimulation behavior. Physostigmine and scopolamine produced the identical effects of tetrabenazine and amphetamine on self-stimulation behavior, but they were ineffective on neuronal activity.