Anxiety and cognitive-related effects of Δ
Δ The objectives of this study were to characterize the effects of intra-accumbens THC in the anterior vs. posterior regions of the NASh during emotional memory formation, sensorimotor gating and anxiety-related behaviours. We performed an integrative series of translational behavioural pharmacological studies examining anxiety, sensorimotor gating and fear-related associative memory formation combined with regionally specific molecular signalling analyses in male Sprague Dawley rats. We report that THC in the posterior NASh causes distortions in emotional salience attribution, impaired sensory filtering and memory retention and heightened anxiety, through a glycogen-synthase-kinase-3 (GSK-3)-β-catenin dependent signalling pathway. In contrast, THC in the anterior NASh produces anxiolytic effects via modulation of protein kinase B (Akt) phosphorylation states. These findings reveal critical new insights into the neuroanatomical and molecular mechanisms associated with the differential neuropsychiatric side effects of THC in dissociable nucleus accumbens sub-regions.