The serotonin (5-HT)1A agonist, LY 165,163, induces contralateral rotation in unilateral substantia nigra-lesioned rats via dopamine receptors.
The serotonin (5-HT)1A agonist, LY 165,163 (1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)-piperazine) , also known as PAPP, has been suggested to exert effects via an interaction with dopamine receptors. Thus, in this study, we examined its ability to induce rotation in rats sustaining unilateral 6-hydroxy-dopamine lesions of the substantia nigra, an in vivo model of dopaminergic activity. In analogy to the direct dopamine (mixed D1/D2) agonist, apomorphine, (0.01-0.63 mg/kg), LY 165,163 (0.16-10.0 mg/kg) dose-dependently elicited robust and sustained contralateral rotation. Its maximal effect was comparable to that of apomorphine and its duration of action more extended. Rotation elicited by LY 165,163 (10.0 mg/kg) was resistant to the 5-HT1A antagonist, (-)-alprenolol. It was also unaffected by the selective D1 antagonist, SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5,tetrahydro-1H-3-be nza zepine) (2.5 mg/kg) or the selective D2 antagonist, raclopride (10.0 mg/kg) when each was administered alone. However, upon joint administration they clearly diminished the effect of LY 165,163. The dopamine antagonist, haloperidol (D2 greater than D1) also reduced the action of LY 165,163. This profile of partial antagonism by mixed D1 and D2 receptor blockade has been reported previously for apomorphine and contrasts to that seen with selective D1 or D2 agonists, the actions of which are completely blocked by D1 or D2 antagonists, respectively. In conclusion, the present data demonstrate that LY 165,163 exerts pronounced rotation in nigral-lesioned rats: this reflects a mixed D1/D2 action rather than an activation of 5-HT1A sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Millan
M J
MJ
FONDAX, Groupe de Recherches Servier, Paris France.
Bervoets
K
K
Mavridis
M
M
D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D012457:Salicylamides / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects* / Q000502:physiology
D001552:Benzazepines; D010879:Piperazines; D011954:Receptors, Dopamine; D012457:Salicylamides; D012702:Serotonin Antagonists; D020891:Raclopride; D000526:Alprenolol; C044643:LY 165163; D016627:Oxidopamine; D006220:Haloperidol; D001058:Apomorphine