Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression.

E Teodorov,D R Fior-Chadi,R Camarini,L F Felício,M F R Ferrari

doi:10.1590/s0100-879x2012007500091

E Teodorov, D R Fior-Chadi + Show 3 more

Open Access

https://doi.org/10.1590/s0100-879x2012007500091

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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.

Highlights

Opioidergic stimuli modulate various sensory systems with behavioral consequences for both male and female mammals [1,2,3,4,5,6,7,8,9]
The present study investigated the effects of U69593, a kappa-opioid receptor agonist, on mu, kappa, and deltaopioid receptor Oprm1, Oprk1, and Oprd1 gene activity in the periaqueductal gray (PAG) of both lactating and virgin female rats
No other significant differences were found in opioid receptor gene expression in lactating rats treated with this drug (Figure 1) in the PAG

Summary

Introduction

Opioidergic stimuli modulate various sensory systems with behavioral consequences for both male and female mammals [1,2,3,4,5,6,7,8,9]. The PAG is known to play important roles in the modulation of nociceptive sensory transmission, regulation of the cardiovascular system [12], vocalization [13], and expression of a variety of behaviors, including defensive [14], sexual [15], maternal [16,17,18], and feeding behaviors [15,19,20]. The PAG occupies a pivotal position in the central nervous system that influences the selection of adaptive behavioral responses. This region receives both limbic information and a vast array of inputs from prefrontal cortical areas [21,22]. Previous studies from our laboratory have suggested an integrative role of opioidergic transmission in the PAG in influencing behavioral selection during lactation [6,23,24,25]

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