Long-term behavioral effects of perinatal exposure to delta 9-tetrahydrocannabinol in rats: possible role of pituitary-adrenal axis.
This work evaluated motor behaviors in adult male and female rats exposed to delta 9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. The possibility that perinatal THC exposure induces sensitization to other drugs of abuse has also been addressed by evaluating morphine place preference conditioning (MPP) in the adult offspring. Maternal exposure to THC resulted in long-term effects on motor behaviors such as rearing, grooming and sniffing, in the adult offsprings of both sexes. Additionally, female offspring exposed to THC showed greater locomotor activity than controls, when measured using an actimeter. THC-exposed males exhibited an increased exploratory behavior in a plus-maze paradigm. When the adult animals were tested for MPP, THC-exposed offspring of both sexes exhibited an enhanced sensitivity to the rewarding effects of a moderate dose of morphine (350 micrograms/kg), an effect which was more marked in the males. These results showed that perinatal exposure to this psychoactive cannabinoid affected motor behaviors in the adult, suggesting a psychomotor activation very similar to that observed after gestational exposure to other drugs of abuse. A possible role of a THC-induced hypothalamus-pituitary-adrenal (HPA) axis activation was also evaluated in the present study. THC-exposed females exhibited higher levels of both corticotropin releasing factor (CRF-41) in the medial basal hypothalamus (MBH) and plasma corticosterone, whereas THC-exposed males showed the lower levels of both endocrine parameters. Since glucocorticoids are important modulators of both brain development, and adult brain function, these results indicate a possible role of HPA axis disturbances in the mediation of the behavioral effects described after perinatal THC exposure.
Rubio
P
P
Instituto Complutense de Drogodependencias (Dept. Psicobiología), Facultad de Psicología, Universidad Complutense, 28223-Madrid, Spain.
Rodríguez de Fonseca
F
F
Muñoz
R M
RM
Ariznavarreta
C
C
Martín-Calderón
J L
JL
Navarro
M
M
D000311:Adrenal Glands / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D013759:Dronabinol / Q000633:toxicity*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar
D013759:Dronabinol