Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function

Abstract

Rationale The use and misuse of prescription opiates in adolescent populations, and in particular, adolescent female populations, has increased dramatically in the past two decades. Given the significant role that opioids play in neuroendocrine function, exposure to opiates during this critical developmental period could have significant consequences for the female, as well as her offspring. Objectives In the current set of studies, we utilized the female rat to model the transgenerational impact of adolescent opiate exposure. Methods We examined locomotor sensitization in response to the dopamine D2/D3 receptor agonist quinpirole in the adult male progeny (F1 and F2 generation) of females exposed to morphine during adolescence. All females were drug-free for at least 3 weeks prior to conception, eliminating the possibility of direct fetal exposure to morphine. Results Both F1 and F2 progeny of morphine-exposed females demonstrated attenuated locomotor sensitization following repeated quinpirole administration. These behavioral effects were coupled with increased quinpirole-induced corticosterone secretion, and up-regulated kappa opioid receptor (KOR) and dopamine D2 receptor (D2R) gene expression within the NAc. Conclusions These results suggest significant modifications in response to repeated D2R activation in the progeny of females exposed to opiates during adolescence. Given the significant role that the D2R plays in psychopathology, adolescent opiate exposure could shift the vulnerability of future offspring to psychological disorders, including addiction. Moreover, that effects are also observed in the F2 generation suggests that adolescent opiate exposure can trigger transgenerational epigenetic modifications impacting systems critical for motivated behavior.

Transgenerational modification of hippocampus TNF-α and S100B levels in the offspring of rats chronically exposed to morphine during adolescence

“…Recently, chronic use of opiates by parents has been reported to produce consequences in children with no direct contact with these substances (35)(36)(37). Epigenetic mechanisms are suggested to be responsible for this phenomenon (38,39).…”

Neuroquantum Theories of Psychiatric Genetics: Can Physical Forces Induce Epigenetic Influence on Future Genomes?

“…In essence, we are asking whether quantum physics can affect through genetic memory, as an example, inducing permanent change in future generations. This point is well researched and indeed shows the transference of epigenetic effects from generation to generation without affecting the germ-cell line (Nestler, 2011 (Byrnes et al, 2013). These behavioral effects were also observed with increased quinpirole-induced corticosterone secretion and kappa opioid receptor upregulation as well as expression of the dopamine D2 receptor (D2R) gene all within the nucleus accumbens.…”

Mechanisms of Non-Genetic Inheritance and Psychiatric Disorders

“…More recently, it was demonstrated that offspring of female rats exposed to morphine during adolescence have alterations in recognition memory, anxiety-like behavior, and social interaction, as well as in opiate sensitivity and tolerance (Byrnes, 2005a, b, Byrnes, 2008Byrnes et al, 2011). Interestingly, some of these effects were further transmitted to the F2 generation (Byrnes et al, 2013). A similar heritable phenotype, resulting from the self-administration of cocaine, was also described in rats (Vassoler et al, 2013).…”