DOPAMINERGIC D1 AND GLUTAMATERGIC AMPA RECEPTORS COOPERATION IN THE LONG.TERM SENSITIZATION TO COCAINE INDUCED BY ACUTE

GARCÍA KELLER C, MARTÍNEZ S, ESPARZA A Y CANCELA LM

HUERTA GRANDE, CORDOBA

Workshop; IRCN ARGENTINE SOCIETY FOR NEUROSCIENCES AND THE ARGENTINE WORKSHOP IN NEUROSCIENCIES; 2009

Several evidences indicate that the administration of the D1 agonist receptor, SKF increased AMPA receptor insertion in the extra synaptic cell surface, phenomenon associated with the sensitization to cocaine. The aim of the present study was to demonstrate the cooperation between D1 and AMPA receptors, in the sensitization induced by stress. Specifically we evaluated the stimulating locomotor properties of cocaine and dopamine release in the nucleus accumbens core (NAcc Core). Male Wistar rats (250?350 g) were restrained for two hours while control animals were left undisturbed in their cages. Twenty-one days after this stress episode all animals were assigned to one of the following experiments: I) Locomotor activity in response to i) AMPA microinyections (0, 0.1 ug/ul, 0.3 ug/ul) in NAcc Core ii) the D1 agonist receptor, SKF38393, (0, 0.5; 1.0 mg/kg i.p.) and iii) the association beetwen SKF 0.5 mg/kg and a subumbral dose of AMPA (0.1 ug/ul administered 10 minutes later in NAcc core). II) Microdialysis: dopamine levels were determinated by HPLC in NAc Core in response to three different concentration of AMPA (1.0; 10.0; 100.0 uM) and  in the expression of sensitization to cocaine (15 mg/kg ip) during the perfusion of the AMPA receptor antagonist, CNQX (1 nmol), ó DMSO (vehicle). These results clearly show the participation of AMPA receptors in the long-lasting sensitization to cocaine following a single restraint stress session. The stimulation of the D1 dopaminergic receptors makes possible the observation of the stimulant effect produced by subumbral doses of AMPA. These results are discussed in the framework of the stimulating effects that the D1 receptors produce in the surface cellular expression of GluR1 (the AMPA receptors subunit) in the stressed animals. Current experiments in our laboratory are attempting to confirm this hypothesis.