Haloperidol, but not apomorphine, differentially affects low response rates of male and female Wistar rats

Amphetamine-induced behavioral differences between male and female rats have been observed in tests for stereotyped behavior, locomotor activity and rotational behavior. It has also been shown that amphetamine differentially affects schedule-controlled behavior of male and female rats. The present experiments were designed to further investigate sex differences in sensitivity to agents which act upon the dopaminergic system. In the first experiment, male and female rats responding on a schedule which maintained low response rates were challenged with different low (less than 0.5 mg/kg) doses of apomorphine. Low doses of apomorphine act on the dopamine receptors on the dopaminergic terminals themselves to inhibit the release of endogenous dopamine. In the second experiment, the same subjects were given different doses of haloperidol, which selectively blocks the post-synaptic dopamine receptors. The results of the present experiments showed that haloperidol, but not apomorphine, differentially affected the behavior of male and female subjects. A behavioral difference between the sexes was thus observed when post-synaptic dopamine receptors were blocked by a dopamine antagonist, but not when dopaminergic stimulation of post-synaptic dopamine receptors was reduced by pre-synaptic inhibition of dopamine release. These results suggest a role for post-synaptic receptor mechanisms in mediating sex differences in sensitivity to dopaminergic agents, although other possible mechanisms remain to be investigated.