Abstract

Induction of the transcription factor ΔFosB was studied to examine neurochemical adaptations produced by repeated opiate administration. The mechanism of this induction was also investigated. The 35- to 37-kDa isoforms of ΔFosB, also referred to as the chronic Fras, were measured in the nucleus accumbens, caudate putamen, and frontal cortex of male Sprague-Dawley rats after either an acute injection of morphine or an escalating dosing schedule of morphine for 10 days. Heroin was also tested to determine whether the findings extend to other opiates. Results from Western blot analysis using an anti-fosB antibody demonstrate that 10-day intermittent escalating dose morphine produced a significant increase in ΔFosB-immunoreactivity in the nucleus accumbens, caudate putamen and frontal cortex, whereas a single injection of morphine had no effect on Fra immunoreactivity. Heroin administered twice daily for 10 days by an intermittent escalating dose schedule also induced ΔFosB in the caudate putamen, but not in the nucleus accumbens or frontal cortex. Daily pretreatment with the selective D1-like dopamine receptor antagonist SCH 23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride] significantly blocked morphine-induced ΔFosB induction in the nucleus accumbens and caudate putamen, but not in the frontal cortex. These results demonstrate that morphine-induced ΔFosB up-regulation in the striatum, but not in the frontal cortex, is modulated by D1 dopamine receptors, suggesting that the mechanisms involved in the up-regulation of these chronic Fras by morphine is brain region-specific.