Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

Abstract

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of U69593 group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female reproduction.

Comparative Transcriptome Analysis Suggests Key Roles for 5-Hydroxytryptamlne Receptors in Control of Goose Egg Production

“…As a receptor for oxytocin, AVPR1A was shown to mediate the secretion of ACTH and PRL by binding AVT to finely regulate ovulation in chickens [31]. Expression levels of OPRK1 were closely related to oocyte maturation [32] and maternal behavior [33]. LPAR3 could interact with multiple reproductive hormones, including progesterone [34], estrogen [35], and prostaglandin [36,37], to affect reproduction.…”

Kappa Opioid System Involvement in Mood and Anxiety Disorders

“…Direct injection of the κ agonist U69593 into the dorsal periaqueductal gray (PAG) stimulated maternal behavior and KOR gene expression. No changes were observed in the δ or μ receptors [43] .…”

Role of steroid hormones and morphine treatment in the modulation of opioid receptor gene expression in brain structures in the female rat

“…The present study evaluated the basal pattern of Oprm1 , Oprk1 , and Oprd1 gene expression in female rat brain sites that are known to be involved in reproductive behavior, including the striatum (i.e., important role in motor patterns during mating and lactation), PAG (i.e., role in nociception, behavioral selection for motivated behaviors, and sexual and maternal behavior), and hypothalamus (i.e., role in the modulation of hormonal aspects) (Sewards and Sewards 2003 ; Moura et al 2010 ; Mota-Ortiz et al 2012 ; Teodorov 2012 ). Studies have shown that estrogen is able to change the action of the opioidergic system in rodents by modulating nociceptive responses to treatment with naloxone, altering the binding of opioid receptors in specific brain regions, and increasing the rate of internalization of these receptors, particularly in morphine studies (Hammer 1990 ; Gordon and Soliman 1996 ; Aloisi and Ceccarelli 1999 ; Micevych et al 2003 ).…”