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The Journal of Neuroscience, March 1, 2003, 23(5):1879

Norepinephrine in the Prefrontal Cortex Is Critical for Amphetamine-Induced Reward and Mesoaccumbens Dopamine Release

Rossella Ventura^{1, 2}, Simona Cabib^{1, 2, 3}, Antonio Alcaro^{1, 2}, Cristina Orsini^{1, 2}, and Stefano Puglisi-Allegra^{1, 2}

¹ Dipartimento di Psicologia, Università "La Sapienza," 00185 Rome, Italy, ² Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, 00179 Rome, Italy, and ³ Istituto di Psicobiologia e Psicofarmacologia, Consiglio Nazionale delle Ricerche, 00137 Rome, Italy

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.

Key words: prefrontal cortex; norepinephrine; conditioned place preference; reward; nucleus accumbens; dopamine

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2351879-07$05.00/0

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