Differential regulation of CDK5 and c-Fos expression by morphine in the brain of Lewis and Fischer 344 rat strains

The aim of this study was to comparatively study cyclin-dependent kinase 5 (CDK5) and c-Fos regulation by morphine in the brains of Lewis and Fischer 344 (F344) rats, which are known to differ in their behavioral sensitivities to several drugs of abuse. Two hours after an acute i.p. administration of morphine (10 mg kg−1) or saline (control), the animals were perfused and their brains prepared for immunohistochemistry. The number of CDK5 immunoreactive cells was significantly higher in the nucleus accumbens (NAC), the locus coeruleus (LC) and the nucleus tractus solitarius (NTS) of saline-injected F344 rats than in those of the Lewis rats. Morphine upregulated CDK5 with a varying pattern depending on the strain and brain area. The effect of the opioid was more marked in the NTS of the Lewis rats and the NAC of the F344 rats. Immunostaining of c-Fos was very low or absent in the control animals and was consistently up-regulated by morphine, especially in the LC and NTS of the F344 rats and the NAC of the Lewis rats. We propose that the acute morphine regulation of CDK5 expression in the NAC may predict the rate of drug intake and/or extinction of drug seeking, while the pattern of c-Fos activation may be more related to the differential acquisition of morphine-seeking behaviors.

► Brain CDK5 and c-Fos show regional differences in rat strains with different opioid sensitivities.
► Acute morphine upregulates CDK5 more markedly in the nucleus accumbens of F344 rats.
► Acute morphine upregulates c-Fos more markedly in the nucleus accumbens of Lewis rats.