Neurobehavioral effects of delta 9-THC and cannabinoid (CB1) receptor gene expression in mice.

The differential sensitivity following the administration of delta 9-THC to 3 mouse strains, C57BL/6, DBA/2 and ICR mice, indicated that some of the neurobehavioral changes may be attributable to genetic differences. The objective of this study was to determine the extent to which the cannabinoid (CB1) receptor is involved in the observed behavioral changes following delta 9-THC administration. This objective was addressed by experiments using: (1) DNA-PCR and reverse PCR; (2) systemic administration of delta 9-THC, and; (3) intracerebral microinjection of delta 9-THC. The site specificity of action of delta 9-THC in the brain was determined using stereotaxic surgical approaches. The intracerebral microinjection of delta 9-THC into the nucleus accumbens was found to induce catalepsy, while injection of delta 9-THC into the central nucleus of amygdala resulted in the production of an anxiogenic-like response. Although the DNA-PCR data indicated that the CB1 gene appeared to be identical and intronless in all 3 mouse strains, the reverse PCR data showed two additional distinct CB1 mRNAs in the C57BL/6 mouse which also differed in pain sensitivity and rectal temperature changes following the administration of delta 9-THC. It is suggested that the diverse neurobehavioral alterations induced by delta 9-THC may not be mediated solely by the CB1 receptors in the brain and that the CB1 genes may not be uniform in the mouse strains.