Amphetamine-Induced Changes in Dendritic Morphology in Rat Forebrain Correspond to Associative Drug Conditioning Rather than Nonassociative Drug Sensitization
Received 25 November 2008; received in revised form 18 December 2008; accepted 19 December 2008. published online 06 February 2009.
Background
Systemic exposure to amphetamine (AMPH) leads to a number of long-lasting neuroadaptations including changes in dendritic morphology in rat forebrain. It remains unknown whether these changes relate to associative drug conditioning or to nonassociative drug sensitization, two forms of plasticity produced by systemic exposure to AMPH.
Methods
We compared the behavioral, neuronal, and morphologic consequences of exposing rats to intraperitoneal (IP) AMPH to those of exposure to AMPH applied to the ventral tegmental area (VTA), infusions that sensitize AMPH-induced locomotion and nucleus accumbens (NAcc) DA overflow but do not produce drug conditioning.
Results
Both IP and VTA AMPH exposure sensitized locomotion and NAcc DA overflow, but only IP AMPH exposure produced conditioned locomotion. Importantly, whereas IP AMPH exposure increased spine density and dendritic length and branching in the NAcc, exposure to VTA AMPH produced the opposite effects. A similar differentiation of effects was observed in cortical areas.
Conclusions
Together these findings suggest that the morphological changes seen following IP AMPH exposure reflect associative drug conditioning rather than nonassociative drug sensitization. The decreases observed in the NAcc of VTA AMPH exposed rats may reflect the inability of these infusions to support conditioning.
aCommittee on Neurobiology, The University of Chicago, Chicago, Illinois
bDepartment of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, Illinois
cDepartment of Pharmacology, Columbia University, New York, New York
dDepartment of Neuroscience, University of Lethbridge, Lethbridge, Canada
Address reprint requests to Paul Vezina, Ph.D., Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, 5841 S. Maryland Avenue, MC 3077, Chicago, IL 60637
ABSTRACT