Effect of early exposure to delta-9-tetrahydrocannabinol on the levels of opioid peptides, gonadotropin-releasing hormone and substance P in the adult male rat brain.
The effects of neonatal exposure to delta-9-tetrahydrocannabinol (THC) on the adult animal brain neurochemistry and pain perception were evaluated. Newborn rat pups were culled to a litter size of 8 (males and females) and treated either with THC (2 mg/kg) or oil (control) daily, during days 1-4 after birth. After weaning, the THC-treated males were housed 4 per cage. During the juvenile period (day 50), the THC-treated animals exhibited significantly lower baseline tail-flick values (a measure of pain perception) than the control. However, as adults, the THC-treated animals exhibited significantly higher sensitivity to pain following 5 mg/kg morphine challenge. Furthermore, the THC-treated animals had significantly elevated beta-endorphin and methionine-enkephalin levels in almost all the brain areas sampled for the study. In addition, the neonatally THC-treated rats exhibited significantly higher levels of substance P (SP) and significantly lower levels of gonadotropin releasing hormone (GnRH) in the anterior hypothalamus-preoptic area. The SP and GnRH levels did not differ among the THC-treated and control animals in the medial basal hypothalamus. The results of this study indicate that even a very low dose of THC administered during the neonatal period has a long-lasting effect on the brain neurochemistry. In particular, neonatal administration of THC appears to alter functioning of the endogenous opioid system.
Department of Anatomy, Tufts University School of Veterinary Medicine, Boston, MA 02111.
A M
AM
Kumar
M
M
Haney
T
T
Becker
M L
ML
Thompson
R M
RM
Kream
K
K
Miczek
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D013759:Dronabinol / Q000494:pharmacology*; D004723:Endorphins / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000187:drug effects*
D004723:Endorphins; D013373:Substance P; D007987:Gonadotropin-Releasing Hormone; D013759:Dronabinol