Amphetamine-induced changes in dendritic morphology in rat forebrain correspond to associative drug conditioning rather than nonassociative drug sensitization.
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.
Singer
Bryan F
BF
Committee on Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA.
Tanabe
Lauren M
LM
Gorny
Grazyna
G
Jake-Matthews
Charmaine
C
Li
Yilin
Y
Kolb
Bryan
B
Vezina
Paul
P
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D003712:Dendrites / Q000187:drug effects*; D049229:Dendritic Spines / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007274:Injections, Intraperitoneal; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects
D000661:Amphetamine; D004298:Dopamine