Paternal exposure to morphine during adolescence potentiates morphine withdrawal in male offspring: Involvement of the lateral paragigantocellularis nucleus.
Age Factors
Animals
Disease Models, Animal
Electrophysiological Phenomena
/ drug effects
Epigenesis, Genetic
/ drug effects
Male
Medulla Oblongata
/ drug effects
Morphine
/ adverse effects
Naloxone
/ pharmacology
Narcotic Antagonists
/ pharmacology
Narcotics
/ adverse effects
Patch-Clamp Techniques
Paternal Exposure
/ adverse effects
Rats
Rats, Wistar
Substance Withdrawal Syndrome
/ etiology
Morphine withdrawal
adolescence
extracellular single-unit recording
intergenerational
lateral paragigantocellularis nucleus
paternal
Journal
Journal of psychopharmacology (Oxford, England)
ISSN: 1461-7285
Titre abrégé: J Psychopharmacol
Pays: United States
ID NLM: 8907828
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
entrez:
28
10
2020
pubmed:
29
10
2020
medline:
5
11
2021
Statut:
ppublish
Résumé
Opiate exposure during adolescence perturbs the brain's maturation process and potentially confers long-term adverse consequences, not only in exposed individuals but also in their posterity. Here, we investigate the outcomes of adolescent paternal morphine exposure on morphine withdrawal profile in male offspring. Male Wistar rats were chronically subjected to 10 days of an escalating regimen of morphine during adolescence. After a 20-day washout period, adult males were allowed to copulate with naïve females. The adult male offspring were tested for somatic and affective components of naloxone-precipitated morphine withdrawal using conditioned place aversion. Moreover, electrical activity of the lateral paragigantocellularis (LPGi) nucleus, which is involved in development of opiate dependence, was recorded in response to a challenge dose of morphine via extracellular single-unit recordings. Morphine-sired offspring exhibited augmented expression of naloxone-induced somatic and affective signs of opiate withdrawal compared to the control saline-sired counterparts. In vivo recording revealed that LPGi neurons displayed heterogeneous responses (inhibitory, excitatory, and no change) to acute morphine administration in both morphine- and saline-sired animals. The morphine-induced discharge inhibition was potentiated in morphine-sired offspring. However, the extent of discharge excitation in response to morphine did not reach significance in these subjects. Moreover, the lack of alteration in maternal behavior toward morphine-sired offspring indicates that this is due to germline-dependent transmission of epigenetic traits across generations. Preconception paternal exposure to morphine during adolescence potentiates opiate withdrawal signs in male offspring which is mediated, at least in part, by epigenetic alteration of LPGi-related brain circuitry.
Sections du résumé
BACKGROUND
Opiate exposure during adolescence perturbs the brain's maturation process and potentially confers long-term adverse consequences, not only in exposed individuals but also in their posterity. Here, we investigate the outcomes of adolescent paternal morphine exposure on morphine withdrawal profile in male offspring.
METHODS
Male Wistar rats were chronically subjected to 10 days of an escalating regimen of morphine during adolescence. After a 20-day washout period, adult males were allowed to copulate with naïve females. The adult male offspring were tested for somatic and affective components of naloxone-precipitated morphine withdrawal using conditioned place aversion. Moreover, electrical activity of the lateral paragigantocellularis (LPGi) nucleus, which is involved in development of opiate dependence, was recorded in response to a challenge dose of morphine via extracellular single-unit recordings.
RESULTS
Morphine-sired offspring exhibited augmented expression of naloxone-induced somatic and affective signs of opiate withdrawal compared to the control saline-sired counterparts. In vivo recording revealed that LPGi neurons displayed heterogeneous responses (inhibitory, excitatory, and no change) to acute morphine administration in both morphine- and saline-sired animals. The morphine-induced discharge inhibition was potentiated in morphine-sired offspring. However, the extent of discharge excitation in response to morphine did not reach significance in these subjects. Moreover, the lack of alteration in maternal behavior toward morphine-sired offspring indicates that this is due to germline-dependent transmission of epigenetic traits across generations.
CONCLUSIONS
Preconception paternal exposure to morphine during adolescence potentiates opiate withdrawal signs in male offspring which is mediated, at least in part, by epigenetic alteration of LPGi-related brain circuitry.
Identifiants
pubmed: 33112218
doi: 10.1177/0269881120953993
doi:
Substances chimiques
Narcotic Antagonists
0
Narcotics
0
Naloxone
36B82AMQ7N
Morphine
76I7G6D29C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM