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.
Kumar
A M
AM
Department of Anatomy, Tufts University School of Veterinary Medicine, Boston, MA 02111.
Haney
M
M
Becker
T
T
Thompson
M L
ML
Kream
R M
RM
Miczek
K
K
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