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Paternal factors in neurodevelopmental toxicology: THC exposure of male rats causes long-lasting neurobehavioral effects in their offspring.

Abstract：

:The potential health risks of cannabis are of growing concern, including effects on reproduction and development. Extensive research has investigated risks associated with maternal exposure to THC during gestation and its impacts on the development of offspring, but little research has been done regarding paternal THC exposure effects prior to conception. We have previously found that paternal THC exposure in rats causes changes in sperm methylation. In an initial study we also showed that a 12-day paternal THC exposure prior to conception alters locomotor activity and impairs cognitive function of their offspring. This study investigated the cross-generational effects of chronic paternal THC exposure in rats (0, 2, or 4 mg/kg/day SC for 28 days) prior to mating with drug naïve females. The offspring of THC-exposed male rats had significant alterations in locomotor activity and cognitive function. Specifically, during adolescence there was significant locomotor hyperactivity in the offspring of males exposed to 2 mg/kg/day of THC. During the novel object recognition task, the controls maintained their relative preference for the novel object across the duration of the ten-min session while the rats whose fathers received THC (2 mg/kg/day) showed a significantly greater drop-off in interest in the novel object during the second half of the session. Learning in the radial-arm maze was significantly delayed in the offspring of males exposed to 4 mg/kg/day of THC. This study shows that premating chronic paternal THC exposure at multiple dose regimens can cause long-lasting detrimental behavioral effects in their offspring, including abnormal locomotor activity and impaired cognitive function. Future studies should investigate the underlying mechanisms driving these aberrant developmental outcomes and seek to identify possible treatments of alleviation in the presence of paternal THC exposure.

journal_name

Neurotoxicology

journal_title

Neurotoxicology

authors

Holloway ZR,Hawkey AB,Pippin E,White H,Wells C,Kenou B,Rezvani AH,Murphy SK,Levin ED

doi

10.1016/j.neuro.2020.01.009

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

57-63

eissn

0161-813X

issn

1872-9711

pii

S0161-813X(20)30017-6

journal_volume

78

pub_type

杂志文章

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