Effects on self-stimulation behavior of drugs influencing dopaminergic neurotransmission mechanisms

Summary

Drugs preferentially influencing dopaminergic neurotransmission mechanisms were administered to rats which lever-pressed to receive electrical stimulation in either the lateral hypothalamus or periaqueductal mesencephalon. The same drug effects were observed regardless of the site of electrical stimulation. Blockade of dopamine receptors by 0.35 or 0.5 mg/kg pimozide reduced self-stimulation rates. Increasing the reward value of the stimulation by doubling of self-stimulation current induced control rates of lever-pressing in animals given 0.35 mg/kg pimozide but not in those receiving 0.5 mg/kg. At doses of 0.75 and 1.5 mg/kg, apomorphine, a putative dopamine receptor stimulator, reduced self-stimulation rates at normal current. Doubling of the stimulation current produced greater than normal rates of lever-pressing at 0.75 mg/kg apomorphine, but at 1.5 mg/kg no such increase in rate was observed. l-DOPA, 75 and 150 mg/kg, also reduced self-stimulation, but doubled current restored rates to control levels at both doses. For comparison purposes, pharmacological effects on predominantly noradrenergic mechanisms were also studied. Inhibition of dopamine-β-hydroxylase by 150 mg/kg disulfiram reduced self-stimulation under normal current, but rates were increased to above control levels with doubled current. That self-stimulation behavior could be reinstated by doubling of current suggests that motor incapacity is not a sufficient explanation for most of the observed reductions in lever-pressing rate. These results further suggest that, in addition to noradrenaline, the integrity of central dopaminergic systems may be essential for the behavioral expression of certain motivational processes.