Interactions between the mu opioid agonist DAMGO and substance P in regulation of the ventral pallidum.

Substance P (SP) increases, and the mu-specific opioid agonist DAMGO decreases neuronal firing within ventral pallidum (VP) of the basal forebrain. This study investigated a possibility that some VP neurons are oppositionally co-regulated by SP and DAMGO using microiontophoresis combined with the extracellular electrophysiological recordings from chloral hydrate-anesthetized rats. SP altered DAMGO's ejection current-response curve, decreasing Emax and slope, and increasing the Ecu50 (ejection current level at which 50% of the maximal response was obtained). The modulation was observed even at low ejection current levels that, when applied alone, were not sufficient to alter neuronal activity (i.e., subthreshold). Also, DAMGO altered the Emax and slope of SP's ejection current-response curve. DAMGO induced these effects even at subthreshold ejection current levels. The responses to each peptide were blocked by a receptor-specific antagonist. These findings demonstrate that SP and mu-activating opioids antagonize each other's effects on VP neuronal firing. Thus, they may interact as physiological antagonists in the regulation of VP-associated functions.