Effects of chronic desipramine treatment on α2-adrenoceptors and μ-opioid receptors in the guinea pig cortex and hippocampus

The existence of a close relation between presynaptic inhibitory α2-adrenoceptor and μ-opioid receptor pathways is well established. Such interplay may occur during chronic conditions that give rise to neuroadaptive changes involving both receptor systems. The aim of this study was to examine the effect of chronic treatment with the tricyclic antidepressant drug, desipramine, on α2-adrenoceptors and μ-opioid receptors in the guinea pig brain. Guinea pigs were treated with 10 mg/kg desipramine, injected i.p. for 21 days, every 24 h. The levels of expression of α2-adrenoceptors and μ-opioid receptors, the G protein receptor regulatory kinase, GRK2/3 and signal transduction inhibitory G proteins in synaptosomes of the guinea pig hippocampus and cortex were evaluated by immunoblotting. Quantitative analysis of α2-adrenoceptor and μ-opioid receptor mRNA levels has been carried out by competitive reverse transcriptase polymerase chain reaction. The expression levels of α2-adrenoceptors and μ-opioid receptors and the respective mRNAs were found unchanged in the cortex, after chronic desipramine treatment. In these experimental conditions α2-adrenoceptor and μ-opioid receptor levels decreased, while the relevant transcripts increased, in the hippocampus. GRK2/3 levels remained unchanged and increased, respectively, in the cortex and the hippocampus, after chronic exposure to desipramine. In the same experimental conditions, Gαi1, Gαi2, Gαo and Gαz levels remained unchanged, while Gαi3 levels decreased, in the cortex; whereas, Gαi1, Gαi2 and Gαi3 levels significantly increased, and Gαo and Gαz levels remained unchanged, in the hippocampus. On the whole, the present data suggest that α2-adrenoceptor and μ-opioid receptor expression and transcription are similarly influenced by chronic treatment with desipramine, in the guinea pig cortex and hippocampus. Furthermore, alterations in the levels of regulatory GRK2/3 and of inhibitory signal transduction G proteins, relevant to activation of both receptor pathways, have been documented. The distinct pattern of adaptations of the different protein studied in response to chronic desipramine treatment in both regions is discussed.