ergoline and des-enkephalin-gamma-endorphin

In rats, the non-opioid beta-endorphin (beta E) fragment desenkephalin-gamma-endorphin (DE gamma E, beta E6-17) antagonizes the hypomotility induced by a small dose of dopamine (DA) receptor agonists. It has been suggested that DE gamma E might act in this respect by a direct or indirect blockade of presynaptically located DA receptors in the nucleus accumbens, thereby causing an increase of DA release. Therefore in the present study the effect of DE gamma E was examined on DA receptor agonist-induced inhibition of the electrically evoked release of previously accumulated [3H]DA from rat nucleus accumbens slices in vitro. The DA receptor agonists apomorphine, LY 171555 and n,n-di-n-propyl-7-hydroxy-2-aminotetralin (DP-7-AT) inhibited in a concentration-dependent manner the electrically evoked release of [3H]DA. The selective D2 receptor antagonist (-)-sulpiride blocked the effects of apomorphine, corroborating that the DA receptor involved is of a D2 type. DE gamma E was tested at several concentrations (10(-9)-10(-6) M) and under various experimental conditions. DE gamma E, by itself, did not affect either the electrically stimulated or the basal release of [3H]DA. The inhibiting effect of DA receptor agonists was slightly reduced by DE gamma E, but this effect was present in some experiments only. It is concluded that DE gamma E does not function as an antagonist for the DA receptor mediating DA release and that the interaction observed in behavioural experiments between DA agonists and DE gamma E does not occur at the level of this receptor.

Topics: Animals; Apomorphine; beta-Endorphin; Dopamine; Ergolines; In Vitro Techniques; Male; Nucleus Accumbens; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Septal Nuclei; Tritium

Injection of small doses of apomorphine, bromocriptine and the new ergoline compound, GYKI-32887 into the nucleus accumbens decreased locomotor activity when rats were tested in a small open field. This effect was observed following injection of 1 pg of these substances; GYKI-32887 being more potent than bromocriptine. The hypolocomotion induced by the ergoline compound could be prevented by local pretreatment with haloperidol (30 pg), fluphenazine (30 pg), sulpiride (10 pg) or desenkephalin -gamma-endorphin (DE gamma E; 100 pg). Large doses of apomorphine and amphetamine, injected into the nucleus accumbens, increased locomotor activity. This behavioural response was antagonized by pretreatment with haloperidol (30 pg), but not with sulpiride (10 pg) or DE gamma E (100 pg or 10 ng). It is concluded that two dopaminergic receptor systems exist in the nucleus accumbens with different sensitivity to apomorphine. One of these receptor systems, which is activated by small doses of apomorphine and ergoline compounds, can be blocked by classical and atypical neuroleptics and by the neuroleptic-like peptide DE gamma E. This may be of relevance to the antipsychotic action of these substances.

Topics: Amphetamine; Animals; Apomorphine; Behavior, Animal; beta-Endorphin; Bromocriptine; Dopamine; Endorphins; Ergolines; Fluphenazine; gamma-Endorphin; Haloperidol; Male; Motor Activity; Nucleus Accumbens; Rats; Rats, Inbred Strains; Septal Nuclei; Sulpiride