Induction of Fos-like immunoreactivity by opioids in guinea-pig brain

In the present study the effects of intracerebroventricular (i.c.v.) administration of 100 nmol of morphine, the selective mu-receptor agonist DAMGO, the delta-receptor agonist DPDPE and the kappa-receptor agonist U50,488H, on the induction of Fos-like immunoreactivity (Fos-LI) in the guinea-pig brain were investigated using immunohistochemical techniques. Guinea-pigs given i.c.v. injection of opioids showed marked increases in the number of Fos-LI nuclei within a large number of brain regions, several of which, including hypothalamic nuclei, paraventricular thalamic nucleus, the amygdala, periaqueductal gray, superior and inferior colliculi, the piriform and entorhinal cortices, have been shown to be activated under stressful or aversive conditions. Pretreatment with the opioid antagonist, naltrexone, before administration of morphine or U50,488H, inhibited Fos-LI induction indicating that the effects of the opioids were mediated by opioid receptors. U50,488H administration resulted in higher numbers of Fos-LI stained neurons compared to morphine in most regions other than the nucleus accumbens and interpeduncular nucleus. Morphine and DAMGO produced significantly higher numbers of Fos-LI neurons in the nucleus accumbens shell region than U50,488H, which may reflect the more powerful reinforcing/rewarding effects of mu-receptor agonists. Thus the present study supports a critical role for the nucleus accumbens shell region in the reinforcing/rewarding effects of opioids.