Modification of dyskinesias following the intrastriatal injection of prostaglandins in the rodent.
The abilities of prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2 alpha to antagonize striatal dopamine function were assessed following bilateral and unilateral injections into the striata of the rat and guinea-pig. Three tests were used to assess the effects of the bilateral injections, ability to antagonize dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin (0.025 mg kg-1 s.c.), ability to antagonize stereotyped behaviour induced by apomorphine (0.5 or 2 mg kg-1 s.c.) and ability to induce catalepsy. Asymmetry/circling behaviour revealed on challenge with apomorphine (0.25 mg kg-1 s.c.) was measured following unilateral injection into the striatum. In the rat, dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin was antagonized by PGE1 (0.001-1 micrograms) and PGE2 (0.00001-1 micrograms) but not by PGD2 or PGF2 alpha (1 microgram). Stereotyped behaviour induced by apomorphine was not antagonized by any of the prostaglandins. A weak catalepsy was induced by PGE1 (1 microgram only), PGE2 (0.001-1 micrograms) and PGD2 (0.001-1 micrograms) but not by PGF2 alpha. Asymmetry and circling behaviour was only observed following the unilateral injection into the striatum of PGE1 and PGD2 (0.01-1 microgram) and challenge with apomorphine. In the guinea-pig the actions of PGE1 and E2 were compared with those of PGF2 alpha. Dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin was antagonized by bilateral injections into the striatum of PGE2 (0.001-1 microgram), but not PGE1 (0.5 micrograms) and PGF2 alpha (1 microgram) but not PGE, (0.5 micrograms) and PGF2 alpha (1 microgram). Similar injections of PGE1, E2 and F2 alpha, all failed to antagonize apomorphine-induced stereotyped behaviour, or to induce catalepsy. PGE, (0.01-0.5 fig) and PGE2 (0.002-1 pg), but not PGF2 alpha, caused asymmetry following unilateral injection into the striatum and peripheral challenge with apomorphine. 5 It is concluded that the major effect in the striatum of the prostaglandins of the E series is to antagonize dyskinetic biting; this action is not shared by other prostaglandins tested, and does not reflect a generalised ability to antagonize striatal dopamine function. It is suggested that the actions of the prostaglandins to modify differentially dopamine-dependent behaviours from the striatum may reflect activity at a site subsequent to the dopamine receptor.
D000527:Alprostadil / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D015237:Dinoprost; D015232:Dinoprostone; D004298:Dopamine / Q000502:physiology; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D007839:Functional Laterality; D006168:Guinea Pigs; D008297:Male; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000008:administration & dosage / Q000494:pharmacology*; D011458:Prostaglandins E / Q000008:administration & dosage / Q000494:pharmacology*; D011460:Prostaglandins F / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors
D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C015842:2-(N,N-dipropyl)amino-5,6-dihydroxytetralin; D015237:Dinoprost; D000527:Alprostadil; D015232:Dinoprostone; D001058:Apomorphine; D015230:Prostaglandin D2; D004298:Dopamine