AT1 receptors blockade attenaute the behavioral sensitization to amphetamine.

PAZ, MC.; ASSIS, A.; CANCELA, LM.; CABRERA, RJ.; BREGONZIO, C

Córdoba

Congreso; Sociedad Argentina de Farmacología Experimental (SAFE); 2006

It is known that psychostimulants induce behavioral sensitization, a neuroadaptation that implicates cellular and molecular changes in the dopaminergic and glutamatergic systems. The evidences support that brain Angiotensin II interacts with dopaminergic neurotransmission through AT1 receptors in striatum and substantia nigra. Male rats (250-300 g) were treated during 5 days with candesartan cilexetil (CV, 3mg/kg v.o.), an AT1 antagonist, and 24h later received one injection of 5 mg/kg amphetamine (Amph). The animals were challenged one or three weeks later  with 0.5 mg/kg of Amph and the locomotor activity registered during 2 hours. Other group of animals without the Amph challenge were sacrificed and the striatum was dissected for 3H-DA release induced by K+(28mM) and amphetamine (10?5M) by in vitro superfussion. An additional group treated with CV were implanted with microdialysis probe in striatum and DA release induced by Amph was quantified by HPLC. We confirmed that locomotor sensitization induced by Amph was higher after 3 weeks of 5 mg/kg Amph injection, and found that this effect was attenuated by previous blockade of the at1 receptor. The antagonist treatment induced a slightly increase in the locomotor activity when tested 3 weeks later. CV attenuated the increase in 3H-DA release induced by K+ in Amph treated group although CV by itself increased it. The data are discussed based in the long-term effects induced by the psychostimulants and AT1 blockers. Additional experiments are needed to clarify the molecular mechanism involved in the brain DA-angiotensin II interaction.