Modulation of motor functions involving the dopaminergic system by AT1 receptor antagonist, losartan.
Growing evidence has indicated the existence of a brain renin angiotensin system and its possible interaction with other putative neurotransmitters and their receptors. In the present study, the effect of losartan, an AT1 receptor antagonist, was studied on the motor functions involving the dopaminergic system. Losartan (5-30 mg/kg) per se decreased locomotor activity without producing motor toxicity. It partially reversed the apomorphine-induced hyperlocomotion and stereotypy in mice, and potentiated neuroleptic-induced catalepsy in rats. On chronic administration (once daily for 21 days) losartan failed to block apomorphine-induced hyperlocomotion, but the inhibition of stereotypic response and potentiation of neuroleptic-induced catalepsy remained unaltered. These observations suggest that losartan inhibited the release of dopamine through AT1 receptor and also suggest the existence of a compensatory mechanism in certain brain region concerned with dopamine motor function.
Raghavendra
V
V
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Chopra
K
K
Kulkarni
S K
SK
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines; D002375:Catalepsy / Q000139:chemically induced; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists; D004357:Drug Synergism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects*; D010546:Perphenazine; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013239:Stereotyped Behavior / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D010546:Perphenazine; D019808:Losartan; D001058:Apomorphine; D004298:Dopamine