Maternal exposure to delta9-tetrahydrocannabinol facilitates morphine self-administration behavior and changes regional binding to central mu opioid receptors in adult offspring female rats.
Opiates and cannabinoids are among the most widely consumed habit-forming drugs in humans. Several studies have demonstrated the existence of interactions between both kind of drugs in a variety of effects and experimental models. The present study has been focused to determine whether perinatal delta9-tetrahydrocannabinol (Delta9-THC) exposure affects the susceptibility to reinforcing effects of morphine in adulthood and whether these potential changes were accompanied by variations in mu opioid receptor binding in brain regions related to drug reinforcement. Adult female rats born from mothers that were daily treated with delta9-THC during gestation and lactation periods, exhibited a statistically significant increase in the rate of acquisition of intravenous morphine self-administration behavior when compared with females born from vehicle-exposed mothers, an effect that did not exist in delta9-THC-exposed male offspring. This increase was significantly greater on the last day of acquisition period. There were not significant differences when the subjects were lever pressing for food. In parallel, we have also examined the density of mu opioid receptors in the brain of adult male and female offspring that were exposed to Delta9-THC during the perinatal period. Collectively, perinatal exposure to delta9-THC produced changes in mu opioid receptor binding that differed regionally and that were mostly different as a function of sex. Thus, delta9-THC-exposed males exhibited a lower density for these receptors than their respective oil-exposed controls in the caudate-putamen area as well as in the amygdala (posteromedial cortical nucleus). On the contrary, delta9-THC-exposed females exhibited higher density of these receptors than their respective oil-exposed controls in the prefrontal cortex, the hippocampus (CA3 area), the amygdala (posteromedial cortical nucleus), the ventral tegmental area and the periaqueductal grey matter, whereas the binding was lower than control females only in the lateral amygdala. These results support the notion that perinatal delta9-THC exposure alters the susceptibility to morphine reinforcing effects in adult female offspring, in parallel with changes in mu opioid receptor binding in several brain regions.
Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Ciudad Universitaria, 28040, Madrid, Spain.
G
G
Vela
S
S
Martín
L
L
García-Gil
J A
JA
Crespo
M
M
Ruiz-Gayo
J J
JJ
Fernández-Ruiz
C
C
García-Lecumberri
D
D
Pélaprat
J A
JA
Fuentes
J A
JA
Ramos
E
E
Ambrosio
D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D013759:Dronabinol / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011619:Psychotropic Drugs / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000378:metabolism; D012054:Reinforcement, Psychology; D012646:Self Administration
D000701:Analgesics, Opioid; D011619:Psychotropic Drugs; D017450:Receptors, Opioid, mu; D009020:Morphine; D013759:Dronabinol