Chronic Δ9-tetrahydrocannabinol administration affects serotonin levels in the rat frontal cortex

Abstract

Adult rats were subjected to chronic treatment with the cannabinoid agonist, Delta9-tetrahydrocannabinol, or with vehicle, and their brains used to analyze the contents of serotonin (5HT) and of its intraneuronal metabolite, 5-hydroxyindolacetic acid (5HIAA). 5HT and 5HIAA contents were not affected by chronic cannabinoid administration in most of the brain regions analyzed. We found a marked increase in 5HT contents in the frontal cortex that was accompanied by no changes in 5HIAA contents. This originated a decrease in 5HIAA/5HT ratio, which suggests a possible reduction in the activity of serotoninergic terminals reaching this cortical area. This effect was not seen after an acute injection of this cannabinoid. The relevance of these observations was that they occurred in a region where changes in serotoninergic transmission have been implicated in the development of depression; therefore, our data support the theory that the cannabinoid system might be a potential target for the treatment of this neuropsychiatric disease.

Genetic Deletion of Fatty Acid Amide Hydrolase Alters Emotional Behavior and Serotonergic Transmission in the Dorsal Raphe, Prefrontal Cortex, and Hippocampus

“…Nevertheless, our electrophysiological experiments revealed a significantly elevated mean DR 5-HT neural activity in FAAH À/À mice that could provide the neurochemical substrate by which anxiolytic-like and antidepressant-like reactivity may be conveyed. Such an impact on 5-HT activity has been observed earlier with URB597 (Gobbi et al, 2005) and a low dose of the CB 1 R agonist, WIN55,212-2 (Bambico et al, 2007), and is consistent with the reported augmentation of the postsynaptic 5-HT content by cannabinoid agonists (Miczek and Dixit, 1980;Holtzman et al, 1969;Sagredo et al, 2006) or URB597 (Gobbi et al, 2005). This increase in 5-HT neural activity has been reliably replicated in other transgenic models of depression and antidepressant activity.…”

Reflection impulsivity in adolescent cannabis users: a comparison with alcohol-using and non-substance-using adolescents

“…Cannabinoids have been shown to interact with 5-HT receptors (Kelaï et al 2006;Kimura et al 1998) and evidence from preclinical studies suggests the involvement of cannabinoid receptors (CB1) in the regulation of serotonergic responses (Lau and Schloss 2008;Mato et al 2007), whereby stimulation of CB1 receptors reduces (Balazsa et al 2008) and inhibits (Best and Regehr 2008;Nakazi et al 2000) 5-HT release. Administration of THC has been shown to decrease serotonergic activity in various brain regions in animal studies (Molina-Holgado et al 1993;Moranta et al 2004;Sagredo et al 2006). Chronic exposure to cannabinoids during adolescence has similarly been shown to attenuate serotonergic activity (Bambico et al 2010) and differentially affect 5-HT1A receptor binding and mRNA expression in adult versus adolescent brains (Zavitsanou et al 2010).…”

Neurochemical effects of the endocannabinoid uptake inhibitor UCM707 in various rat brain regions

“…The contents of serotonin and its metabolite were analyzed using HPLC with electrochemical detection according to our previously published method (Sagredo et al, 2006). Briefly, homogenates were diluted in ice-cold 0.4 N perchloric acid containing 0.4 mM sodium disulfite and 0.90 mM EDTA.…”