Inhibition of nNOS not only prevents but also reverses cocaine sensitization

GABACH, LAURA A; ARTUR DE LA VILLARMOIS, EMILCE; PÉREZ, MARIELA F

Oviedo

Congreso; XV Congreso de la Sociedad Española de Neurociencias.; 2013

Sociedad Española de Neurociencias

Behavioral sensitization it is known as the increased sensitivity to locomotor stimulating effect after repeated psychostimulants administration, and is believed to be relevant to drug addiction and craving in humans. Repeated cocaine induces behavioral sensitization in a 50% of treated male Wistar rats and it can modulate synaptic plasticity in the hippocampus which is an important brain region for some associative learning processes occurring during addiction. Nitric oxide is a neurotransmitter involved in a broad range of effects in the central nervous system including synaptic plasticity and complex behavioral responses among others. We have previously demonstrated a key role of nNOS/NO/sGC/cGMP signaling pathway in the development of cocaine sensitization and in the associated enhancement of hippocampal synaptic plasticity (HSP). In the present work, we attempted to determine whether the inhibition of nNOS after sensitization reverse this behavioral effect and the associated hippocampal synaptic plasticity. We administered 5 daily cocaine injections (i.p.) to 35 days old Wistar rats, followed by 5 daily 7-nitroindazole (nNOS inhibitor) injections (i.p.). We tested development of cocaine sensitization (in vivo) and the threshold for LTP in hippocampus (in vitro) as indicator of synaptic plasticity. The results show that inhibition of nNOS after repeated cocaine administration reversed behavioral sensitization and the highest level of plasticity induced by repeated cocaine. Therefore, considering that nNOS/NO/sGC/cGMP signaling pathway in the brain can initiate, contribute or exacerbate addictive behaviors, the interference of this pathway, even after development of cocaine sensitization, could be a useful tool to reduce susceptibility to relapse.