Is the Nociception Mechanism Altered in Offspring of Morphine-Abstinent Rats?

Abstract

To investigate the effect of parental drug abuse on children, nociception, electrophysiological alteration, mRNA expression of opioid receptors, and expression of certain intracellular proteins in offspring of morphine-abstinent rats were studied. Adult male and female animals received water-soluble morphine for 21 days. Ten days after the last morphine administration, animals were placed for mating in 4 groups as follows: healthy (drug naive) female and male, morphine-abstinent female and healthy male, morphine-abstinent male and healthy female, morphine-abstinent male and morphine-abstinent female. Their adult male offspring were tested for nociception, neuronal discharge in nucleus accumbens (NAC) and prefrontal cortex (PFC). Our results showed that nociception in male offspring of all morphine-abstinent parent(s) groups was significantly reduced, compared with the control group. In the offspring of morphine-abstinent parent(s) groups, sensitivity to the antinociceptive effect of morphine was enhanced in chronic as well as in acute phases of the formalin test. Neuronal electrical activity reduced in the offspring of the morphine-exposed parent(s) in NAC as well as PFC regions. Moreover, our findings show that opioid receptors' expressions (µ, κ, and δ) increased in NAC of the litter of morphine-abstinent parent(s), compared with the control group. In addition, the expression of κ receptors was remarkably increased in the PFC in morphine-abstinent parent group, relative to the control group. The phosphorylated levels of extracellular regulated kinase 1/2 and cyclic adenosine monophosphate responsive element binding protein were significantly higher in the offspring of the morphine-abstinent parent(s) than the control group in the NAC. Our results indicated that endogenous opioid is altered in offspring of the morphine-exposed parent(s) and that heritage has a major role.

Perspective: This study showed that nociception was reduced in offspring of morphine-abstinent rat(s) and also these litters had a low level of neuronal firing rate, and enhanced opioid receptors expression, especially in the NAC. Because these offspring are more sensitive to the analgesic effect of morphine, clinicians should consider this issue to manage the dosage of morphine for treating pain in children with an abstinent parent(s).

Keywords: Morphine; cyclic adenosine monophosphate responsive element binding; electrophysiology; opioid receptors expression; pain.