176 Opioid Modulation of Ventral Pallidal Inputs T. CELESTE NAPIER a AND IGOR MITROVIC b Department of Pharmacology and Experimental Therapeutics, Neuroscience and Aging Institute, Division for Research on Drugs of Abuse, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA ABSTRACT: While the ventral pallidum (VP) is known to be important in re- laying information between the nucleus accumbens and target structures, it has become clear that substantial information processing occurs within the VP. We evaluated the possibility that opioid modulation of other transmitters con- tained in VP afferents is involved in this process. Initially, we demonstrated that opioids hyperpolarized VP neurons in vitro and suppressed spontaneous firing in vivo. The ability of opioids to modulate other transmitters was deter- mined using microiontophoretically applied ligands and extracellular record- ings of VP neurons from chloral hydrate–anesthetized rats. With neurons that responded to iontophoresed opioid agonists, the ejection current was reduced to a level that was below that necessary to alter spontaneous firing. This “sub- threshold” current was used to determine the ability of mu opioid receptor (μR) agonists to alter VP responses to endogenous (released by electrical acti- vation of afferents) and exogenous (iontophoretically applied) transmitters. μR agonists decreased the variability and enhanced the acuity (e.g., “signal-to- noise” relationship) of VP responses to activation of glutamatergic inputs from the prefrontal cortex and amygdala. By contrast, μR agonists attenuated both the slow excitatory responses to substance P and GABA-induced inhibitions that resulted from activating the nucleus accumbens. Subthreshold opioids also attenuated inhibitory responses to stimulating midbrain dopaminergic cells. These results suggest that a consequence of opioid transmission in the VP is to negate the influence of some afferents (e.g., midbrain dopamine and ac- cumbal GABA and substance P) while selectively potentiating the efficacy of others (e.g., cortical and amygdaloid glutamate). Interpreted in the context of opiate abuse, μR opioids in the VP may serve to diminish the influence of rein- forcement (ventral tegmental area and nucleus accumbens) in the transduction of cognition (prefrontal cortex) and affect (amygdala) into behavior. This may contribute to drug craving that occurs even in the absence of reward. Since the seminal paper by Heimer and Wilson 1 introducing the concept of the ventral striatopallidal system, the anatomy and the morphology of afferents to the ventral pallidum (VP) have enjoyed considerable attention (see other chapters in this volume). Pioneered by Mogenson, 2 a handful of laboratories now have described the a Address for correspondence: T. Celeste Napier, Ph.D., Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, 2160 South 1st Avenue, Maywood, Illi- nois 60153. Voice: 708-216-8427; fax: 708-216-6596; cnapier@luc.edu b Current address: Department of Anatomy and W. M. Keck Center for Integrative Neuro- science, University of California San Francisco, San Francisco, CA 94143.