Locomotor hyperactivity in the rat after infusion of muscimol and [D-Ala2]Met-enkephalin into the nucleus basalis magnocellularis. Possible interaction with cortical cholinergic projections.

Locomotor activity in the rat was studied after infusion of GABAergic and enkephalinergic agonists into the nucleus basalis magnocellularis (NBM) of the forebrain. The experiments were designed to find out whether pharmacological blockade of cholinergic neurons in the NBM had similar behavioral effects to those observed after lesion of the same structure. Three experiments were carried out. In the first experiment, infusion of the GABAergic agonist muscimol (50 ng) into the NBM led to a marked locomotor hyperactivity. In the second experiment, it was shown that muscimol-induced locomotor response was reduced by pretreatment with the GABAergic antagonist picrotoxin (3 mg/kg). Further, locomotor hyperactivity was also observed after injection of the indirect GABA agonist, ethanolamine-o-sulfate (50 micrograms) into the NBM. The third experiment was designed to investigate the relationship between the blockade of NBM cholinergic neurons and the development of locomotor hyperactivity. The locomotor hyperactivity produced by the cholinergic antagonist scopolamine (0.4 mg/kg) was increased two-fold after infusion of 10 ng muscimol into the NBM. This dose of muscimol on its own had no effect on locomotor behavior. Similar enhancement of the locomotor response to that found with GABAergic agonists was observed after infusion of [D-Ala2]Met-enkephalinamide (2.5 micrograms) into the NBM. This enkephalin mediated locomotor response was blocked by the opiate antagonist naloxone (2 mg/kg). Pharmacological manipulations of the afferent inputs to the NBM could therefore be of value in studies on the behavioral role of cholinergic neurons in the NBM.