Desenkephalin-γ-endorphin restores the impaired sensitivity of hypophysectomized rats to small doses of apomorphine

Abstract

Hypophysectomized male rats, tested 7 days after removal of the pituitary, showed a reduced sensitivity to small doses of apomorphine. In these rats, subcutaneous (s.c.) treatment with apomorphine (25, 100 or 250 μg/kg) did not elicit any reduction in locomotor activity measured 5 min after injection in contrast to that observed in sham-operated control rats. The enhancement of locomotor activity and stereotyped behavior, 20 min after the s.c. administration of apomorphine, was similar in hypophysectomized rats and in control animals. Prolactin does not seem to be implicated in this altered sensitivity, since hyperprolactinaemia induced by pituitary homografts under the kidney capsule did not change the response to apomorphine in hypophysectomized rats. Chronic treatment with desenkephalin-γ-endorphin (DEγE), a β-endorphin fragment with neuroleptic-like properties, administered s.c. twice a day for 7 days at the dose of 10 μg/rat, restored the sensitivity to small doses of apomorphine in the hypophysectomized rats. The data suggest that removal of the pituitary leads to impaired sensitivity of presumably presynaptically located dopamine receptors mediating the effects of small doses of apomorphine without altering the sensitivity of postsynaptically located dopamine receptors that mediate the hypermotility and stereotypy induced by apomorphine. This impaired sensitivity to low doses of apomorphine could be restored by DEγE but not by prolactin, supporting the conclusions from previous experiments that DEγE and prolactin may selectively interfere with pre- and postsynaptic dopamine receptors respectively.