Acute and chronic actions of morphine on induction of immediate-early genes: Plastic changes and serotonergic involvement
Description
Morphine produces a characteristic pattern of immediate-early gene (IEG) expression within the caudate-putamen (CPu). A set of experiments was designed to assess the involvement of the medial thalamus, the serotonin (5-HT) system, and the effect of morphine in post-dependent rats The medial thalamus provides the CPu with glutamate. The importance of these projections was assessed by infusing the mu opioid receptor antagonist, beta-funaltrexamine (beta-FNA), into the medial thalamus prior to systemic morphine. beta-FNA attenuated morphine-induced IEG expression in the CPu The 5-HT system is thought to be involved in the acute actions of morphine. To determine if projections from the DRN are involved in morphine-induced IEG expression, beta-FNA, was unilaterally infused at the level of the DRN, prior to morphine. beta-funaltrexamine prevented morphine-induced behavior, in addition to significantly attenuating morphine-induce IEG expression in the CPu. To assess the involvement of the 5-HT2C receptor, a selective antagonist, RS 102221, was administered prior to morphine. RS-102221 did not alter morphine-induced IEG expression in the CPu. To determine whether the 5-HT3 receptor is involved in morphine-induced c-Fos expression in the rat CPu, a selective antagonist, MDL 72222, was administered prior to morphine. MDL 72222 potentiated morphine-induced IEG expression To determine whether there was an alteration in IEG expression in post-dependent rats, an acute challenge morphine treatment was administered after withdrawal from chronic morphine. Compared to an acute morphine, the induction of c-Fos was increased in the dorsolateral CPu following a challenge injection at 7 days of withdrawal. Induction of c-Fos in the central medial nucleus of the thalamus (CM) was blunted at 7 days of withdrawal. An increase in JunB expression was observed following 7 days of withdrawal in the entire CPu. Thus, altered patterns of IEG expression occur in the forebrain of post-dependent rats upon morphine challenge These studies demonstrate the involvement of the medial thalamus, the serotonergic system and provide evidence indicating that post-dependent rats display an altered pattern of IEG expression following challenge treatment