title: Effects of amphetamine on dopamine release in the rat nucleus accumbens shell region depend on cannabinoid CB1 receptor activation.
abstract: The psychostimulant drug amphetamine is often prescribed to treat Attention-Deficit/Hyperactivity Disorder. The behavioral effects of the psychostimulant drug amphetamine depend on its ability to increase monoamine neurotransmission in brain regions such as the nucleus accumbens (NAC) and medial prefrontal cortex (mPFC). Recent behavioral data suggest that the endocannabinoid system also plays a role in this respect. Here we investigated the role of cannabinoid CB1 receptor activity in amphetamine-induced monoamine release in the NAC and/or mPFC of rats using in vivo microdialysis. Results show that systemic administration of a low, clinically relevant dose of amphetamine (0.5mg/kg) robustly increased dopamine and norepinephrine release (to ∼175-350% of baseline values) in the NAC shell and core subregions as well as the ventral and dorsal parts of the mPFC, while moderately enhancing extracellular serotonin levels (to ∼135% of baseline value) in the NAC core only. Although systemic administration of the CB1 receptor antagonist SR141716A (0-3mg/kg) alone did not affect monoamine release, it dose-dependently abolished amphetamine-induced dopamine release specifically in the NAC shell. SR141716A did not affect amphetamine-induced norepinephrine or serotonin release in any of the brain regions investigated. Thus, the effects of acute CB1 receptor blockade on amphetamine-induced monoamine transmission were restricted to dopamine, and more specifically to mesolimbic dopamine projections into the NAC shell. This brain region- and monoamine-selective role of CB1 receptors is suggested to subserve the behavioral effects of amphetamine.
authors.affiliation: Dept. of Biomonitoring & Sensoring, University of Groningen, Groningen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Kleijn
authors.forename: J
authors.initials: J
authors.lastname: Wiskerke
authors.forename: T I F H
authors.initials: TI
authors.lastname: Cremers
authors.forename: A N M
authors.initials: AN
authors.lastname: Schoffelmeer
authors.forename: B H C
authors.initials: BH
authors.lastname: Westerink
authors.forename: T
authors.initials: T
authors.lastname: Pattij
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*
chemical_list: D043884:Receptor, Cannabinoid, CB1; D000661:Amphetamine; D004298:Dopamine