Relapsing back to drug taking remains a significant problem among recovering addicts. As cues once associated with repeated drug administration can initiate drug craving during prolonged periods of abstinence, similar mechanisms of synaptic plasticity may underlie learning and addiction. We propose that associative learning correlates with synaptic plasticity in the glutamatergic system of the ventral pallidum (VP). We will consider this possibility by testing three hypotheses that form the Specific Aims of this grant. Hypothesis 1: The VP is sufficient and necessary for morphine-induced behaviors and requires excitatory amino acids. Studies for this Aim will soon be completed. Hypothesis 2: The AMPA/NMDA receptor ratio will be increased in rats that demonstrate morphine-induced associative learning. We will use whole-cell patch clamp to determine the respective contribution of each receptor type in VP neurons. Hypothesis 3: Glutamte. NMDA. and AMPA function is unregulated in VP neurons following morphine-associated place preference. We will measure action potentials of VP neurons following stimulation of the BLA excitatory input and determine if firing is modulated by microiontophoretic application of agonists and antagonists in the VP.
