Paternal exposure to morphine during adolescence induces reward-resistant phenotype to morphine in male offspring. 2019

Maryam Azadi, and Hossein Azizi, and Abbas Haghparast
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

The developing brain is extremely sensitive to drugs during adolescence. The devastating impacts of opioid abuse in this critical period not only do involve individuals but also are witnessed in the subsequent generations. Therefore, what is recognized as the population susceptible to the effects of opioid abuse could be much greater in number. In this study, we explored the transgenerational effects of morphine exposure in adolescent stage on morphine reward in male offspring through the patriline. Male Wistar rats underwent 10 days of incremental doses of morphine administration during adolescence; the broad spectrum of neurobehavioral alterations in rat adolescence is akin to that of human adolescence. Thereafter, following a 20-day wash-out period, adult males copulated with naïve females. The adult male offspring were examined for morphine (0, 1, 2 and 5 mg/kg)-induced conditioned place preference (CPP). Moreover, the spontaneous activity of ventral tegmental area (VTA) dopamine (DA) neurons was investigated utilizing extracellular single-unit recording technique. Our results demonstrated that paternal morphine exposure prior to conception leads to the development of a tolerance to the rewarding effects of morphine at the low dose of 1 mg/kg (rightward shift in dose-effect curve). Furthermore, morphine-sired rats elicited a decrease in spontaneous burst firing of VTA DA neurons (burst event frequency, bursting activity and burst duration) compared to saline-sired ones. Hence, our study has provided evidence that paternal morphine exposure during adolescence alters the rewarding effects of morphine in male offspring. This effect may be mediated in part by a decrease in phasic activation of VTA DA neurons.

UI MeSH Term Description Entries
D008297 Male Males
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D003214 Conditioning, Classical Learning that takes place when a conditioned stimulus is paired with an unconditioned stimulus. Reflex, Conditioned,Classical Conditioning,Classical Conditionings,Conditioned Reflex,Conditionings, Classical
D004361 Drug Tolerance Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL. Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012201 Reward An object or a situation that can serve to reinforce a response, to satisfy a motive, or to afford pleasure. Rewards
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D017557 Ventral Tegmental Area A region in the MESENCEPHALON which is dorsomedial to the SUBSTANTIA NIGRA and ventral to the RED NUCLEUS. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the NUCLEUS ACCUMBENS. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of SCHIZOPHRENIA. Area Tegmentalis Ventralis,Ventral Tegmental Area of Tsai,Area Tegmentalis Ventrali,Tegmental Area, Ventral,Tegmentalis Ventrali, Area,Tegmentalis Ventralis, Area

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