The Role of Amygdalar Mu-Opioid Receptors in Anxiety-Related Responses in Two Rat Models

Abstract

Amygdala opioids such as enkephalin appear to play some role in the control of anxiety and the anxiolytic effects of benzodiazepines, although the opioid receptor subtypes mediating such effects are unclear. This study compared the influences of mu-opioid receptor (MOR) activation in the central nucleus of the amygdala (CEA) on unconditioned fear or anxiety-like responses in two models, the elevated plus maze, and the defensive burying test. The role of MORs in the anxiolytic actions of the benzodiazepine agonist diazepam was also examined using both models. Either the MOR agonist [D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO), or the MOR antagonists Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) or beta-funaltrexamine (FNA) were bilaterally infused into the CEA of rats before testing. The results show that microinjection of DAMGO in the CEA decreased open-arm time in the plus maze, whereas CTAP increased open-arm behaviors. In contrast, DAMGO injections in the CEA reduced burying behaviors and increased rearing following exposure to a predator odor, suggesting a shift in the behavioral response in this context. Amygdala injections of the MOR agonist DAMGO or the MOR antagonist CTAP failed to change the anxiolytic effects of diazepam in either test. Our results demonstrate that MOR activation in the central amygdala exerts distinctive effects in two different models of unconditioned fear or anxiety-like responses, and suggest that opioids may exert context-specific regulation of amygdalar output circuits and behavioral responses during exposure to potential threats (open arms of the maze) vs discrete threats (predator odor).