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Is the Nociception Mechanism Altered in Offspring of Morphine-Abstinent Rats?
Ghorbangol Ashabi1, Mitra-Sadat Sadat-Shirazi2, Ardeshir Akbarabadi3
1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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).
Insights
Parental drug abuse in rats alters offspring
Area of Science:
- Neuroscience and Pharmacology
- Developmental Biology
- Genetics and Epigenetics
Background:
- Parental drug abuse can have profound and lasting effects on offspring development.
- Understanding the mechanisms by which parental morphine exposure impacts offspring is crucial for public health.
- Previous research has not fully elucidated the long-term neurobiological consequences of parental opioid exposure.
Purpose of the Study:
- To investigate the effects of parental morphine abstinence on offspring's nociception, electrophysiology, and gene expression.
- To examine alterations in opioid receptor and intracellular protein expression in offspring of morphine-exposed rats.
- To determine the role of heritage in mediating the effects of parental drug abuse on offspring.
Main Methods:
- Adult rats were administered morphine for 21 days to induce abstinence.
- Offspring from various mating groups (control, single-parent abstinence, dual-parent abstinence) were tested.
- Nociception, neuronal discharge in the nucleus accumbens (NAC) and prefrontal cortex (PFC), and protein/receptor expression were analyzed.
Main Results:
- Offspring of morphine-abstinent parents exhibited reduced nociception and enhanced sensitivity to morphine's analgesic effects.
- Reduced neuronal electrical activity was observed in the NAC and PFC of offspring from exposed parents.
- Increased expression of opioid receptors (µ, κ, δ) in the NAC and κ receptors in the PFC was noted, along with elevated phosphorylated ERK1/2 and CREB levels in the NAC.
Conclusions:
- Parental morphine exposure significantly alters endogenous opioid systems and neurobiological functions in offspring.
- Heritage plays a critical role in transmitting the effects of parental drug abuse across generations.
- Clinicians should consider these findings when managing pain in children with a history of parental opioid abstinence due to altered morphine sensitivity.
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