Contributions of the GABAergic system of the prelimbic cortex and basolateral amygdala to morphine withdrawal-induced contextual fear.

ABSTRACT

Morphine withdrawal can trigger disruptions in neuronal pathways involved in the modulation and expression of anxiety and fear-related behaviors, particularly those involved in associative learning. When it comes to contextual fear, specific subdivisions of the medial prefrontal cortex (mPFC) regulate the expression of defensive behaviors through projections to specific amygdala (AM) nuclei, such as the prelimbic cortex (PrL). The basolateral nucleus (BLA) of the AM has been shown to be involved in the modulation and expression of associative memories of fear, including those associated with opiate withdrawal-related aversive events. The purpose of this study is to determine the role of GABA mechanisms in the PrL and BLA in startle potentiation and freezing behavior caused by morphine-precipitated withdrawal. Our findings show that morphine withdrawal promotes the emergence of contextual conditioned fear in animals when they are exposed to the same environment where the withdrawal sessions were performed. This suggests that the neural circuits underlying the organism's response to conditioned stressors and the circuits modulating the negative affective states induced by drug withdrawal may overlap. The pharmacological manipulation of GABAergic neurotransmission in the PrL and BLA can reverse contextual fear in morphine-withdrawn rats, an effect that appears to be mediated, at least in part, by GABAA receptors.