Cannabinoid receptor binding and mRNA levels in several brain regions of adult male and female rats perinatally exposed to delta9-tetrahydrocannabinol.
The present study was designed to elucidate whether perinatal delta9-tetrahydrocannabinol (delta9-THC) exposure results in changes in cannabinoid receptor binding and mRNA levels in adulthood. Most of the brain areas studied, including the basal ganglia, the cerebellum, the limbic structures, and most of the hippocampal regions exhibited no changes in cannabinoid receptor binding and mRNA levels in adulthood as a consequence of the perinatal delta9-THC exposure. However, some subtle changes could be appreciated in specific regions, although their physiological relevance seems uncertain. For example, delta9-THC-exposed males exhibited a small decrease in binding in the superficial layer of the cerebral cortex, an effect that was not seen in delta9-THC-exposed females and in mRNA levels for both males and females. In the CA2 layer of the Ammon's horn, there was an increase in mRNA levels of delta9-THC-exposed animals, although this was statistically significant only in males. However, the more marked and probably relevant changes were seen in the arcuate nucleus, where delta9-THC-exposed males exhibited an increase in binding, whereas this tended to decrease in delta9-THC-exposed females. In an additional experiment, we analyzed the motor response of these animals to a challenge with SR141716, a specific antagonist for cannabinoid receptors. The delta9-THC-exposed animals tended to show a higher response to SR141716 challenge, with changes apparently more marked in delta9-THC-exposed females, although they did not reach statistical significance. In summary, perinatal cannabinoid exposure does not appear to significantly alter cannabinoid receptor binding and mRNA expression in the brain of adult rats, as well as the motor response caused by the blockade of these receptors with a specific antagonist. There were some changes in the status of cannabinoid receptors but they were very small and, hence, of debatable physiological relevance. The most significant of these effects was the increase in binding observed in the arcuate nucleus of delta9-THC-exposed males.
García-Gil
L
L
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Romero
J
J
Ramos
J A
JA
Fernández-Ruiz
J J
JJ
D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000196:embryology*; D001923:Brain Chemistry; D002186:Cannabinoids / Q000009:adverse effects*; D013759:Dronabinol / Q000009:adverse effects*; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism*; D012737:Sex Factors; D019956:Stereotypic Movement Disorder / Q000139:chemically induced
D002186:Cannabinoids; D012333:RNA, Messenger; D011955:Receptors, Drug; D013759:Dronabinol