title: Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine release.
abstract: Increasing evidence points to a major involvement of cortical areas in addictive mechanisms. Noradrenergic transmission in the medial prefrontal cortex (mpFC) has been shown to affect the motor effects of amphetamine, although there is no evidence of its involvement in the rewarding effects of this psychostimulant. The present experiments were aimed at investigating the possibility of a selective involvement of prefrontal cortical norepinephrine (NE) in the rewarding-reinforcing effects of amphetamine. To do so, we evaluated the effects of mpFC NE selective depletion in mice of C57BL/6J inbred strain, a background commonly used in molecular approaches that is known to be highly susceptible to the rewarding effects of the psychostimulant. In a first set of experiments, we demonstrated the absence of amphetamine-induced conditioned place preference in mice bearing prefrontal NE depletion. In a second series of experiments, we demonstrated that the same lesion dramatically reduced amphetamine-induced mesoaccumbens dopamine release as measured by intracerebral microdialysis. These results indicate that noradrenergic prefrontal transmission, by allowing increased dopamine release in the nucleus accumbens induced by amphetamine, is a critical factor for the rewarding-reinforcing effects of this drug.
authors.affiliation: Dipartimento di Psicologia, Università La Sapienza, 00185 Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Ventura
authors.forename: Simona
authors.initials: S
authors.lastname: Cabib
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcaro
authors.forename: Cristina
authors.initials: C
authors.lastname: Orsini
authors.forename: Stefano
authors.initials: S
authors.lastname: Puglisi-Allegra
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects
chemical_list: D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D016627:Oxidopamine; C043425:vanoxerine; D000661:Amphetamine; D004298:Dopamine; D009638:Norepinephrine