LACK OF GABAB1 SUBUNIT OF THE GABAB RECEPTOR INCREASES THE AVERSIVE EFFECT ASSOCIATED TO MORPHINE WITHDRAWAL IN MICE

VARANI ANDRÉS P.; PEDRÓN VALERIA T.; BALERIO GRACIELA N.; AON AMIRA J.; CANERO ELIANA M.

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Previous studies from our laboratory have shown an interaction between the opioidergic and GABAergic systems in a pharmacological approach. The GABAB receptor agonist, baclofen, was able to prevent the disphoric effect associated to morphine (MOR) withdrawal in mice. In order to continue exploring this interaction we aimed to study this aversive effect associated to MOR withdrawal by the conditioned place aversion (CPA) paradigm in a genetic approach, using mice lacking the GABAB1 subunit of the GABAB receptor (GABAB1 knockout) and their wild type littermates (WT). CPA consists in 3 phases: preconditioning, aversive conditioning and post conditioning. After preconditioning, mice of both genotypes were rendered dependent by an intraperitoneal (i.p.) injection of MOR (2 mg/kg), twice daily for 9 consecutive days. A control group received chronic saline (SAL) injections. On the 10th day, the conditioning phase started: 60 min after the last MOR injection, the withdrawal syndrome was precipitated by the administration of the opioid receptor antagonist, naloxone (3 mg/kg, i.p.) and mice were left to explore one of the context of a conditioning box for 30 min. The next day, mice were injected with SAL 60 min after the last MOR injection and placed in the opposite context for 30 min. Post conditioning phase was performed 24 hs after the last conditioning sesion. The results showed that MOR withdrawal was able to induce aversive effect in both WT (p