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 so me of the neurobehavioral changes may be attributable to genetic diffe rences. The objective of this study was to determine the extent to whi ch the cannabinoid (CB1) receptor is involved in the observed behavior al changes following Delta(9)-THC administration. This objective was a ddressed by experiments using: (1) DNA-PCR and reverse PCR; (2) system ic administration of Delta(9)-THC, and; (3) intracerebral microinjecti on of Delta(9)-THC. The site specificity of action of Delta(9)-THC in the brain was determined using stereotaxic surgical approaches. The in tracerebral microinjection of Delta(9)-THC into the nucleus accumbens was found to induce catalepsy, while injection of Delta(9)-THC into th e central nucleus of amygdala resulted in the production of an anxioge nic-like response. Although the DNA-PCR data indicated that the CB1 ge ne appeared to be identical and intronless in all 3 mouse strains, the reverse PCR data showed two additional distinct CB1 mRNAs in the C57B L/6 mouse which also differed in pain sensitivity and rectal temperatu re changes following the administration of Delta(9)-THC. It is suggest ed that the diverse neurobehavioral alterations induced by Delta(9)-TH C may not be mediated solely by the CB1 receptors in the brain and tha t the CB1 genes may not be uniform in the mouse strains.