The overall goal of the proposed research is to characterize cellular and molecular mechanisms underlying the actions of opiates in the rat septal area. The septal area is part of the septo-hippocampal complex and contains amongst the highest densities of mu and delta opiate receptor subtypes in the brain, comparable to that in the nucleus accumbens. While opiate actions have been extensively studied in the hippocampus and in the nucleus accumbens, the septal area has remained relatively unexplored. Opiate actions in the septal area are likely to be significant with respect to the addictive properties of opiates as the septal area supports self-stimulation behavior and is anatomically linked to reward pathways. The proposed research will use electrophysiological methods in conjunction with anatomical and molecular approaches to study opiate actions in the medial and lateral divisions of the septal area.
The specific aims of the proposed research are:
AIM 1. Identification and characterization of opiate-responsive neurons in the septal area. Opiate-responsive neurons in brain slices of the septal area will be characterized using electrophysiological anatomical, and neuropharmacological approaches. In the medial septum and the diagonal band of Broca (MSDB), effects of opiates will be tested on antidromically- identified cholinergic and GABAergic septo-hippocampal projection neurons. In the lateral septum (LS), studies will focus on orthodromically- identified GABAergic somatospiny projection neurons which receive input from hypothalamic enkephalinergic fibers.
AIM 2. Effects of opiates on synaptic interactions within the septal area. The effect of opiates on synaptic interactions within each of the two septal divisions (e.g. interactions between cholinergic and GABAergic MSDB neurons) and between the lateral and medial septal divisions (e.g. interactions between GABAergic neurons in the two divisions) will be investigated. It is postulated that these synaptic interactions will determine the net effect of opiates on septal projection neurons.
AIM 3. Analysis of the signal transduction pathways underlying opiate actions in the septal area. The ionic mechanisms underlying opiate responses in the septal area, role of specific G proteins and opiate interactions with second messenger pathways will be investigated. In summary, the proposed studies on the basic mechanisms underlying the physiological actions of opiates on septal neurons will provide a framework for understanding the contribution of the septal area to the addictive properties of opiates.
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