Neuronal responses of the globus pallidus to systemic administration of d-amphetamine: investigation of the involvement of dopamine, norepinephrine, and serotonin

Abstract

Systemic administration of d-amphetamine (d-AMP) caused significant increases in the unit activity of spontaneously firing neurons in the rat globus pallidus. Intravenous injection of 0.2 mg/kg of d-AMP produced an average increase of 32% while a cumulative dose of 6.4 mg/kg of d-AMP increased cell firing 81% above base line control. The excitatory effects of d-AMP on pallidal cells were effectively blocked and reversed by haloperidol. Increasing intravenous doses of l-amphetamine (l-AMP), totaling 12.8 mg/kg, caused a slight excitation of pallidal neurons. The average maximum increase was 18.3%. Minor rate-elevating effects were also observed after systemic administration of desmethylimipramine and clonidine. The serotonin uptake inhibitor, fluoxetine, produced varied changes in firing frequencies. Pretreatment with reserpine and alpha-methyl-p-tyrosine significantly attenuated the d-AMP-induced increase in pallidal activity. These results suggest that dopamine plays a prominent role in mediating the stimulatory effects of d-AMP on the firing rates of a population of globus pallidus cells in gallamine-paralyzed rats.