PARTICIPATION OF NITRIC OXIDE SIGNALING WITHIN THE MEDIAL PREFRONTAL CORTEX IN THE EXPRESSION OF COCAINE SENSITIZATION

PONCE BETI MF; MARIELA F. PÉREZ.

Mar del Plata

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2022; 2022

The medial prefrontal cortex (mPFC), a brain region that regulates cognitive functions and reward motivated behaviors, is implicated in the neuropathological mechanisms of drug addiction. Nitric oxide (NO) is a neurotransmitter that plays a major role in initiating and maintaining the behavioral effects of psychostimulant drugs, such as cocaine (COC) sensitization (SENS). In fact, acute COC administration increases NO release in the mPFC, which was prevented by nitric oxide synthase type-1 enzyme (NOS-1) inhibition by systemic administration of a selective inhibitor (7-nitroindazole, 7NI). Furthermore, systemic 7NI injection during repeated COC administration prevented the persistent increase in membrane excitability of mPFC pyramidal neurons and long term potentiation in hippocampus (HP) after short-term withdrawal. However little is known about the contribution of NO signaling within the mPFC to the expression of COC SENS. Objective: to determine whether intra mPFC NOS-1 inhibition after COC SENS reverses its expression. Material and methods: mPFC cannulated male Wistar rats (42 days old) received five daily COC injections (i.p) and locomotor activity was monitored on days 1 and 5 to evaluate development of COC SENS. On day 6, animals received intra-mPFC administration of 7NI (0.1 μmol/μl; 0.5 μl/side) or DMSO. On day 7, rats received an i.p. challenge of SAL or COC and locomotor activity was measured. Results: sensitized rats showed a significant increase in locomotor activity on day 5 compared to day 1 within the group (p<0.05 Two-Way RM-ANOVA), but no differences were found in locomotor activity on day 7 compared to day 5 after 7NI intra-mPFC administration (p>0.05, preliminary results). Conclusions: it seems that NOS-1 inhibition within m-PFC after COC SENS is not able to reverse its expression, as it was previously observed after intra-HP administration. Probably, NO signaling within the mPFC does not play a fundamental role in the expression of COC SENS.