Treatment with steroid hormones and morphine alters general activity, sexual behavior, and opioid gene expression in female rats

AimsPrevious studies have shown that brain opioid peptides exert an inhibitory influence on gonadotropin secretion. Different types of brain opioids, such as β-endorphin, enkephalin, and dynorphin, exert their actions by binding to specific opioid receptors (i.e., μ, δ, and κ, respectively). The present study determined the effects of chronic treatment with morphine in female rats with pharmacologically induced estrus on behavior and opioid receptor gene and protein expression in the hypothalamus, striatum, and periaqueductal gray.Main methodsFemale ovariectomized rats treated with estrogen + progesterone received 3.5 mg/kg morphine once per day for 6 days. We evaluated general activity, sexual behavior, Oprm1, Oprd1, and Oprk1 gene expression, and μ opioid receptor (MOR), δ opioid receptor (DOR), and κ opioid receptor (KOR) protein expression in the hypothalamus, striatum, and periaqueductal gray in adult virgin female ovariectomized rats.Key findingsChronic morphine treatment increased locomotion and grooming behavior, decreased immobility time, decreased sexual behavior, and decreased the lordosis quotient. The molecular biology results showed that morphine treatment increased Oprm1 gene and MOR protein expression in the striatum and decreased KOR protein expression in the hypothalamus in animals that were assessed for general activity. The animals that were evaluated for sexual behavior exhibited an increase in Oprm1 expression in the periaqueductal gray and increase in KOR expression in the striatum.SignificanceThese results suggest that both opioid system activation and sex hormones alter behavioral and molecular patterns in ovariectomized rats within a relatively short period of time.