Gene expression of opioid and dopamine systems in mouse striatum: effects of CB1 receptors, age and sex

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 (δ-OR); mu-opioid receptor (μ-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) δ-OR was age-dependent (higher in old). (3) μ-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, μ-OR, D 4 ) and old males (PPDYN, δ-OR, D 2 , D 3 , D 4 ).