Butorphanol dependence increases hippocampal kappa-opioid receptor gene expression.

Butorphanol is a synthetic opioid agonist/antagonist analgesic agent, which exerts its effects mainly via kappa-opioid receptors. Characterizations of the gene expression levels of the mRNA for and protein levels of the kappa-opioid receptor in different brain regions of rats are essential for investigating possible mechanisms in the development of physical dependence on and withdrawal from butorphanol. Animals were rendered dependent by intracerebroventricular (i.c.v.) infusion of butorphanol (26 nmol/microl/hr) via osmotic minipumps for 3 days. Rats were sacrificed immediately (dependent group) or 7 hr after discontinuation of i.c.v. butorphanol infusion (withdrawal group). Expression levels of the mRNA for the kappa-opioid receptor, as detected by reverse transcription-polymerase chain reaction followed by Southern blot analysis, were significantly increased in the cerebral cortex, striatum, and midbrain, including thalamus, hippocampus, and pons, in animals dependent on butorphanol. In both dependent and withdrawal groups, Western blot analysis of kappa-opioid receptor protein levels showed significant increases in the amygdaloid nucleus, paraventricular thalamus, and thalamus. However, in the withdrawal group, there were significant decreases in the hippocampus and cortical regions, including the frontal, parietal, and temporal cortex. Regional changes in the mRNA for and protein levels of the kappa-opioid receptor focus attention on highly special roles for this receptor in the development of physical dependence on and the expression of withdrawal from butorphanol dependence.