Conditioned place aversion to morphine withdrawal in mice lacking the GABAB1 subunit of GABAB receptor

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

Berlín

Congreso; 11th FENS Forum of European Neuroscience; 2018

Previous studies from our laboratory have shown an interaction between the opioidergic and GABAergic systems from a pharmacological approach. The GABAB receptor agonist, baclofen, was able to prevent the conditioned place aversion (CPA) induced by morphine (MOR) withdrawal in mice. AIM: To study the CPA induced by MOR withdrawal using mice lacking the GABAB1 subunit of the GABAB receptor (GABAB1 KO) and their wild type littermates (WT). METHODS: CPA consists in 3 phases: pre-test, conditioning and test. After pre-test, mice from both genotypes were rendered dependent by intraperitoneal (ip) injection of MOR (2mg/kg), twice daily for 9 days. A control group received chronic saline (SAL) injections. Conditioning phase (10th day): 60 min after the last MOR injection, the withdrawal syndrome was precipitated by the administration of an opioid receptor antagonist, naloxone (3 mg/kg, ip) and mice were left to explore one 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. Test was performed 24hs after the last conditioning session. RESULTS: MOR withdrawal was able to induce CPA in both WT and GABAB1 KO mice but the intensity of CPA was significantly higher in GABAB1 KO mice compared to their WT littermates. CONCLUSION: GABAB receptors could have a significant role in modulating the aversive state induced by MOR withdrawal. In addition, GABAB receptors could be a potential therapeutic target to treat MOR addiction.