Rationale: Endocannabinoid, opioid, and dopamine systems interact to exhibit cannabinoid receptor neuromodulation of opioid peptides and D(4) dopamine receptor gene expression in CB(1)-cannabinoid-deficient mouse striatum.
Objective: Using CB(1)-transgenic mice, we examine primary age-sex influences and interactions on opioid and dopamine system members' gene expression in striatum.
Materials and methods: Real-time quantitative polymerase chain reaction was used to analyze gene expression of opioid peptides [preproenkephalin (PPENK); preprodynorphin (PPDYN)], opioid receptors [delta-opioid receptor (delta-OR); mu-opioid receptor (micro-OR)] and dopamine receptor subtypes (D(1) through D(5)) in male/female CB(1)(+/+)/CB(1)(-/-) mice striata at two adult ages [young (60-90 days); old (140-300 days)].
Results: (1) Increased PPENK and PPDYN, owing to genotype [CB(1)(+/+) vs. CB(1)(-/-)], depended on sex. When genotype-independent, they depended on sex (PPENK) or age (PPDYN). (2) delta-OR was age-dependent (higher in old). (3) micro-OR, owing to genotype, was age-dependent [higher in old CB(1)(-/-) males]. When genotype-independent, it depended on sex (higher in females). (4) Female D(1) was genotype-independent and age-dependent, while male D(1) was higher in old over young CB(1)(+/+) mice. (5) D(5), owing to genotype, was sex-dependent [higher in young female CB(1)(-/-) mice]. (6) D(2), genotype-independent, was higher in old over young male mice. (7) Young female D(3) was higher in CB(1)(-/-) over CB(1)(+/+) mice. Male D(3) was age-dependent (higher in old mice). (8) D(4), owing to genotype, was sex-dependent [higher in CB(1)(-/-) over CB(1)(+/+) females]. Genotype-independent D(4) was sex-dependent in young mice (higher in females) and age-dependent in males (higher in old).
Conclusions: Greater striatal expression is genotype-dependent in females (opioid-peptides, D(3), D(4), D(5)) and genotype-independent in both females (PPENK, mu-OR, D(4)) and old males (PPDYN, delta-OR, D(2), D(3), D(4)).