Cannabinoid administration increases 5HT1A receptor binding and mRNA expression in the hippocampus of adult but not adolescent rats

• Published in: Neuroscience Vol. 169; no. 1; pp. 315 - 324
• Main Authors: Zavitsanou, K, Wang, H, Dalton, V.S, Nguyen, V
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 11.08.2010; Elsevier
• Subjects: adolescence; Age Factors; Animals; Biological and medical sciences; cannabinoid; Cannabis; Dentate Gyrus - drug effects; Dentate Gyrus - metabolism; Dronabinol - administration & dosage; Dronabinol - analogs & derivatives; Dronabinol - pharmacology; Drug Administration Schedule; Fundamental and applied biological sciences. Psychology; Gyrus Cinguli - metabolism; hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; HU210; Male; Medical sciences; Neurology; Neuropharmacology; Pharmacology. Drug treatments; Psychodysleptics: hallucinogen; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1A - genetics; Receptor, Serotonin, 5-HT1A - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Septal Nuclei - metabolism; Serotonin - metabolism; serotonin receptors; Somatosensory Cortex - metabolism; Vertebrates: nervous system and sense organs; DG; CTXdo; cannabinoid; CTX; PND; THC; Sept; CA1; primary somatosensory cortex; analysis of variance; ANOVA; postnatal day; hippocampus DG; Cing; serotonin receptors; delta-9-tetrahydrocanabinol; hippocampus; primary somatosensory cortex layers IV–VI; cingulate cortex; hippocampus CA1; AMY; septum; VMH; TE; CTXup; adolescence; HU210; amygdaloid complex; primary somatosensory cortex layers I–III; hypothalamus ventromedial; tissue equivalent; Human; Rat; Rodentia; Central nervous system; Serotonine receptor; Cannabinoid; Gene expression; Encephalon; Vertebrata; Mammalia; Animal; Cannabinoid receptor; Adolescent; Hippocampus
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.04.005

Abstract The endocannabinoid and serotonin systems share a high level of overlap in terms of the physiological processes that they regulate, however, little is known about their functional interactions particularly during adolescence, a vulnerable period for both the development of psychosis and for initiation to substance use. In the present study, the effects of cannabinoid treatment on serotonin 5HT1A receptor density and mRNA expression were investigated in two age groups: Adolescent (postnatal day 35) and adult (postnatal day 70) rats were injected with the synthetic cannabinoid HU210 (25, 50 or 100 μg/kg) or vehicle for 1, 4 or 14 days and sacrificed 24 h after the last injection. 5HT1A receptor density was measured in different brain regions using [3 H]8-OH-DPAT quantitative autoradiography whereas mRNA expression was measured in adjacent brain sections. Higher levels of both serotonin 5HT1A receptor binding and mRNA expression were observed in limbic regions in adolescent control animals compared to adults. 5HT1A receptor density was increased by 23% in the CA1 region of the hippocampus of adult rats treated with 100 μg/kg HU210 for 4 days compared to vehicle treated controls. The same treatment increased mRNA expression by 27% and by 14% in the CA1 region and dentate gyrus of the hippocampus respectively. 5HT1A receptor density was increased by 22% in the CA1 of adult animals treated with 50 μg HU210, by 26% in the dentate gurus of adult rats treated with 100 μg for 14 days. By contrast, 5HT1A receptor density or mRNA expression was not affected in the brain of adolescent animals in any of the brain regions examined. These results suggest that cannabinoid treatment has differential effects on serotonin-related neurochemistry in adolescent compared to adult rats. The effects in the adult brain may compromise hippocampal function and could account for the cognitive deficits seen in habitual heavy cannabis users.