Differential treatment regimen-related effects of cannabinoids on D1 and D2 receptors in adolescent and adult rat brain

Animal studies suggest differential effects of cannabinoids on dopamine-related behaviours in adolescence and adulthood however few studies have investigated the underlying neurochemical effects of cannabinoids during adolescence. The aim of the present study was to compare the effects of treatment with the synthetic cannabinoid, HU210, on dopamine receptor density in adolescent and adult rats. Adolescent (postnatal day (PND) 35) and adult (PND 70) rats received a single dose of 100 μg/kg HU210 or 25, 50 or 100 μg/kg HU210 for 4 or 14 days. Dopamine D1 receptor (D1R) or D2 receptor (D2R) density was measured in the medial and lateral (CPUL) caudate putamen, nucleus accumbens, olfactory tubercle (TU) and substantia nigra (D1R only) using in vitro autoradiography. D1R and D2R densities were 1.6–1.7- and 1.1–1.4-fold higher respectively in adolescent control rats compared to adults. In adult rats, D1R density was increased by 1.2- and 1.3-fold (p < 0.05) in CPUL and TU respectively compared to controls, after 14 days of HU210 treatment. A significant overall effect of treatment (p < 0.05) on D2R density was also observed in adults after the single dose and 4 and 14 days administration of HU210. In adolescents, an overall effect of treatment on D1R density after a single exposure to HU210 was seen (p = 0.0026) but no changes in D1R or D2R densities were observed in other treatment groups. These results suggest that the adolescent rat brain does not display the same compensatory mechanisms activated in the adult brain following cannabinoid treatment.

Research highlights▶ D1 and D2 densities were greater in adolescent control rats than in adults. ▶ Chronic HU210 in adults caused increases in D1 density in caudate putamen and olfactory tubercle. ▶ In adults, HU210 had a significant effect on D2 density in all treatment groups. ▶ In adolescent rats, only the single dose of HU210 had an effect on D1 density. ▶ In adolescent rats, D2 receptor density was unaffected in all HU210 treatment groups.