Desenkephalin-gamma-endorphin is an antagonist of the hyperactivity response induced by infusion of dopamine into the nucleus accumbens of rat and ventral striatum of marmoset.
The ability of desenkephalin-gamma-endorphin (DE gamma E; ORG5878) to antagonise a raised limbic dopamine function was investigated in the rat and common marmoset. Dopamine was infused for 13 days directly into the nucleus accumbens of the rat and ventral striatum of the marmoset and increased locomotor activity. Such increases in both the rat and marmoset were antagonised by the subcutaneous injection of DE gamma E, administered in a range 10-500 micrograms/kg (t.i.d.), during the 13 day period of infusion of dopamine. Treatment with dopamine alone or in combination with DE gamma E failed to influence the level of spontaneous locomotor activity after discontinuing treatment. In contrast, in experiments performed in the rat, the level of spontaneous locomotor activity was increased 2- to 3-fold after cessation of a regimen of infusion of dopamine and haloperidol. The increases in activity were antagonised by DE gamma E (50 and 100 micrograms/kg t.i.d., s.c., for 2 days). In additional experiments in the marmoset, using animals initially selected as "high activity" responders to challenge with (-)N-n-propylnorapomorphine, the infusion of dopamine caused a reversal in responsiveness to the stimulant effects of (-)N-n-propylnorapomorphine on locomotor activity some 2-4 weeks after discontinuing the infusion of dopamine. The administration of fluphenazine (0.01-2.5 mg/kg b.d.), during the infusion of dopamine, failed to prevent the subsequent change in responsiveness to (-)N-n-propylnorapomorphine, whereas a regimen of dopamine and DE gamma-E (25-100 micrograms/kg t.i.d.) prevented such changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Costall
B
B
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, West Yorkshire, U.K.
Domeney
A M
AM
Naylor
R J
RJ
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D002143:Callitrichinae; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D005260:Female; D005476:Fluphenazine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000502:physiology*; D001615:beta-Endorphin / Q000494:pharmacology*
D015259:Dopamine Agents; D018492:Dopamine Antagonists; C009074:N-n-propylnorapomorphine; D001615:beta-Endorphin; C033558:des-enkephalin-gamma-endorphin; D006220:Haloperidol; D001058:Apomorphine; D005476:Fluphenazine; D004298:Dopamine