Opioid modulation of ventral pallidal inputs.

While the ventral pallidum (VP) is known to be important in relaying 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 contained 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 determined using microiontophoretically applied ligands and extracellular recordings 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 "subthreshold" current was used to determine the ability of mu opioid receptor (microR) agonists to alter VP responses to endogenous (released by electrical activation of afferents) and exogenous (iontophoretically applied) transmitters. microR 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, microR 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 accumbal GABA and substance P) while selectively potentiating the efficacy of others (e.g., cortical and amygdaloid glutamate). Interpreted in the context of opiate abuse, microR opioids in the VP may serve to diminish the influence of reinforcement (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.