Unilateral striatal dopamine denervation: reduced motor inhibitory effects of dopamine antagonists revealed in models of asymmetric and circling behaviour.
Circling and asymmetric behaviours to apomorphine (dopamine agonist/antagonist) challenge were studied in rats with unilateral striatal electrolesions or 6-hydroxydopamine (6-OHDA) lesions, each induced by combined lesions at 3 striatal locations, to allow an assessment of drug action on 'normal' receptors in the intact striatum or 'supersensitive' receptors in the lesioned striatum respectively. The minimally effective dose of 6-OHDA (given in the presence of DMI and tranylcypromine) to cause functional change was 3 X 8 micrograms, with 3 X 32 micrograms providing maximal change. Electrolesions were shown histologically to be confined to striatal tissue, and dopamine depletions caused by 6-OHDA were selective for the striatum. Temporal differences were recorded for onset of asymmetry and circling behaviour, both between behaviours and between lesions. Thus, asymmetry developed during the 2nd-4th days after 6-OHDA lesion but circling developed more abruptly on postoperative days 10-12. In contrast, both asymmetry and circling behaviours were apparent from the first day following electrolesion. The dose-dependent effects of apomorphine were apparent at much lower doses in 6-OHDA lesioned than electrolesioned rats. This potency difference was also demonstrated for two further dopamine agonists, 2-di-n-propylamino-5,6-dihydroxytetralin and SK & F 38393. In contrast, the agonist-induced asymmetric and circling behaviours of electrolesioned rats were some 9-44 times more sensitive than those of 6-OHDA lesioned rats to antagonism by the neuroleptic agents haloperidol, alpha-flupenthixol and oxiperomide, although tiapride antagonism was very similar in both the electrolesioned and 6-OHDA-lesioned rats.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000502:physiology*; D003714:Denervation; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D004558:Electric Stimulation; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine; D011187:Posture; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology*; D014191:Tranylcypromine / Q000494:pharmacology
D018492:Dopamine Antagonists; D006892:Hydroxydopamines; D014191:Tranylcypromine; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine