Modulation by fluoxetine of striatal dopamine release following Δ⁹‐tetrahydrocannabinol: a microdialysis study in conscious rats

Abstract

1. The present study was undertaken to investigate the effect of Delta9-tetrahydrocannabinol (Delta9-THC) and possible serotoninergic involvement on the extracellular level of dopamine (DA) in the striatum using microdialysis in conscious, freely-moving rats. 2. A dose-dependent increase in striatal DA release occurred after i.v. administration of 0.5 - 5 mg kg-1 Delta9-THC when compared with vehicle (n=5 - 8, P<0.05). Maximum increases, ranging from 42.1+/-5. 4% to 97.4+/-5.9% (means+/-s.e.mean) of basal levels occurred 20 min after Delta9-THC. This effect was abolished by pretreatment with the cannabinoid CB1 receptor antagonist, SR 141716 (2.5 mg kg-1 i.p.). 3. Pretreatment with fluoxetine (10 mg kg-1 i.p.) abolished the Delta9-THC-induced DA release. Fluoxetine 10 mg kg-1 i.p. administered 40 min after Delta9-THC had no significant effect on Delta9-THC-induced DA release. However, fluoxetine perfused locally into the striatum by adding it to the microdialysis perfusion fluid (10 microM) 40 min after Delta9-THC significantly potentiated the Delta9-THC-induced DA release (n=6 - 8, P<0.05). 4. These results suggest that DA release induced by Delta9-THC is modulated by serotoninergic changes induced by fluoxetine, the effect of which depends on the time of its administration relative to that of Delta9-THC. Fluoxetine induces an acute increase in extracellular 5-HT through reuptake inhibition, which can activate autoreceptors which may decrease serotoninergic neuronal activity. This may be the reason fluoxetine pretreatment abolished the Delta9-THC-induced DA release. The potentiation of Delta9-THC-induced DA release by fluoxetine perfusion added 40 min after Delta9-THC may be due to an acute increase in 5-HT produced by reuptake inhibition.

Cannabinoid receptors are localized to noradrenergic axon terminals in the rat frontal cortex

“…However, in vivo microdialysis studies have shown that systemic administration of cannabinoid agonists can increase neurotransmitter efflux as well. For example, cannabinoid agonists increase extracellular dopamine (Tanda, Pontieri et al 1997;Malone and Taylor 1999), glutamate (Ferraro, Tomasini et al 2001) and acetylcholine (Acquas, Pisanu et al 2000) efflux in the frontal cortex (Pistis, Ferraro et al 2002). Our previous findings add to this growing literature by showing that systemic administration of a synthetic CB1 agonist stimulates norepinephrine release.…”

Adolescent Cannabis Exposure Alters Opiate Intake and Opioid Limbic Neuronal Populations in Adult Rats

“…Such alteration in the mOR coupling would be expected to potentiate dopamine levels in forebrain areas such as the NAc and caudate-putamen, considering that stimulation of these midbrain receptors would disinhibit the inhibitory GABAergic regulation on dopamine cell firing (Johnson and North, 1992). The potential involvement of the dopamine system in regulating the long-term effects of THC should be directly addressed in future studies with the current animal model, but studies in the literature have already substantiated enhanced striatal dopamine levels following THC administration (Malone and Taylor, 1999;Tanda et al, 1997). Interestingly, heroin intake behavior was directly correlated with agonist activation of the mOR GTP coupling and this observation was specifically localized to the NAc shell.…”

Prejunctional and peripheral effects of the cannabinoid CB1 receptor inverse agonist rimonabant (SR 141716)

“…Whereas in vitro studies in the rat striatum showed rimonabant-sensitive inhibitory effects of exogenous cannabinoids (Cadogan et al 1997;Kathmann et al 1999), in vivo studies in the same tissue reported stimulatory effects (Malone and Taylor 1999). The cannabinoid receptors in the latter model may be located on GABAergic interneurones synapsing with the dopaminergic perikarya.…”