The long-term goal of this project is to understand how endogenous opioid peptides in the mammalian forebrain contribute to the regulation of stress-related behavior and hypoalgesia. Neural systems exist within the brain and spinal cord which are capable of modulating the transmission of pain, and the amygdaloid complex appears to be a critical forebrain structure involved in the activation of these systems in response to environmental stressors. The objective of the present series of experiments is to evaluate in detail our recent observation that microinjection of kappa opioid receptor agonists into the amygdala results in the modulation of a spinally-mediated nociceptive reflex in the pentobarbital-anesthetized rat. Animals will be anesthetized and prepared for measurement of heart rate and mean arterial blood pressure. Cannulae will be stereotaxically positioned over target brain structures and opioid receptor agonists will be applied to the amygdala. The latency of the animals reflex response to radiant heat applied to the tail is measured at 2 min intervals throughout the procedure. Specifically, we propose to [1] determine the type(s) of opioid receptors involved by characterizing the dose-response functions of 3 highly selective opioid receptor agonists (DAGO, DPDPE, U50,488H), [2] correlate dose-related elevations in tail flick latency with changes in heart rate and blood pressure, [3] localize the critical population of opioid receptors within the amygdala and [4] assess the involvement of descending antinociceptive systems by using lidocaine to block neural activity at critical brainstem sites (periaqueductal gray, nucleus raphe magnus) following opioid microinjection in the amygdala. These experiments will provide very important information about the function of forebrain opioid receptors and the mechanisms through which endogenous antinociceptive systems may be activated in the behaving animal.
