¹Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago School of Medicine, Maywood, IL, USA

Correspondence: Dr TC Napier, Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago School of Medicine, 2160 South 1st Avenue, Maywood, IL 60153, USA. Tel: +1 708 216 8427; Fax: +1 708 216 6596; E-mail: cnapier@lumc.edu

Received 9 February 2005; Revised 3 June 2005; Accepted 29 June 2005; Published online 10 August 2005.

Abstract

Activation of -opioid receptors in the ventral pallidum (VP) is important for the induction of behavioral sensitization to morphine in rats. The present study was designed to ascertain if neurons within the VP demonstrate sensitization at a time when morphine-induced behavioral sensitization occurred (ie 3 or 14 days after five once-daily injections of 10 mg/kg i.p. morphine) in rats. Western blotting was used to evaluate transcription factors altered by opiates, CREB and FosB. CREB levels did not change in the VP, but there was a significant decrease in levels of its active, phosphorylated form (pCREB) at both 3- and 14-days withdrawal. FosB levels were elevated following a 3-day withdrawal, but returned to normal by 14 days. This profile also was obtained from nucleus accumbens tissue. In a separate group of similarly treated rats, in vivo electrophysiological recordings of VP neuronal responses to microiontophoretically applied ligands were carried out after 14-days withdrawal. The firing rate effects of local applications of morphine were diminished in rats withdrawn from i.p. morphine. Repeated i.p. morphine did not alter GABA-mediated suppression of firing, or the rate enhancing effects of the D1 dopamine receptor agonist SKF82958 or glutamate. However, VP neurons from rats withdrawn from repeated i.p. morphine showed a higher propensity to enter a state of depolarization inactivation to locally applied glutamate. Overall, these findings reveal that decreased pCREB in brain regions such as the VP accompanies persistent behavioral sensitization to morphine and that this biochemical alteration may influence the excitability of neurons in this brain region.