title: Short-term development of behavioral sensitization to amphetamine requires N-methyl-D-aspartate- and nicotinic-dependent mechanisms in the nucleus accumbens.
abstract: Repeated administration of psychostimulant drugs, such as amphetamine, induces an enhanced behavioral response to subsequent drug challenge. This behavioral sensitization is proposed to model the increased drug craving observed in human psychostimulant abusers. Current thinking is that the ventral tegmental area, but not the nucleus accumbens, plays a critical role in the development of behavioral sensitization. Here, we report that the concomitant blockade of glutamatergic and nicotinic ionotropic receptors in the core of the nucleus accumbens blocks the development of behavioral sensitization to amphetamine and further abolishes the increase in extracellular dopamine release induced by amphetamine in the nucleus accumbens. These findings demonstrate that the development of behavioral sensitization to amphetamine depends, in addition to the well-known role of the ventral tegmental area, on glutamatergic and nicotinic-dependent mechanisms in the core of the nucleus accumbens and further indicate that the dopaminergic mesolimbic pathway must be viewed as a single coordinated system of critical importance in the development of behavioral sensitization to psychostimulant drugs.
authors.affiliation: Université de Caen, Boulevard Henri Becquerel, Caen, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Degoulet
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Rostain
authors.forename: Jacques H
authors.initials: JH
authors.lastname: Abraini
authors.forename: Hélène N
authors.initials: HN
authors.lastname: David
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000209:etiology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D018733:Nicotinic Antagonists; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D016202:N-Methylaspartate; D000661:Amphetamine