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Sensitization by ventral pallidal DAMGO: lack of cross-sensitization to morphine

Repeated injections of morphine into the ventral pallidum of laboratory rats results in the development and expression of motor sensitization. Although morphine and [D-Ala2, N-MePhe4, Gly(ol)5]-enkephalin (DAMGO) both activate &mgr;-opioid receptors, their influence on receptor-mediated signaling differs; therefore, we determined if they differentially influenced ventral pallidal-mediated motor sensitization. Repeated intraventral pallidal injections of DAMGO led to the development of motor sensitization and this behavior persisted for at least 18 days. When DAMGO-sensitized rats were challenged with a morphine treatment (either in the ventral pallidum or systemically), the resulting motor response was similar to that seen in rats with a history of intrapallidal saline, that is, cross-sensitization did not occur. As DAMGO and morphine likely activate different arms of the heterologous signal transduction system associated with &mgr;-opioid receptors, these observations may reflect behavioral consequences of biased agonism at these receptors.