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Neuroscience
Cluster Scientific Retreat |
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Graduate Student, Committee on Neurobiology Drug-induced neuroadaptations
underlying associative and non-associative plasticity Systemic exposure to amphetamine
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 non-associative drug sensitization, two forms of
plasticity produced by systemic exposure to amphetamine. We compared the behavioral,
neuronal, and morphologic consequences of exposing rats to intraperitoneal
(IP) amphetamine to those of exposure to amphetamine applied to the ventral tegmental area (VTA), infusions that sensitize
amphetamine-induced locomotion and nucleus accumbens
(NAcc) DA overflow but do not produce drug
conditioning. As expected, both IP and VTA amphetamine exposure sensitized
locomotion and NAcc DA release, but only IP
amphetamine exposure produced conditioned locomotion. Importantly, whereas IP
amphetamine exposure increased spine density and dendritic
length and branching in the NAcc, exposure to VTA
amphetamine produced the opposite effects. A similar differentiation of effects
was observed in cortical areas. The protein cdk5 blocks
cocaine-mediated increases in NAcc dendritic spine density while preserving sensitized locomotor responding. Here we show that cdk5
inhibition during drug-paired environmental exposure blocks conditioned
locomotion while preserving sensitization. Thus, blockade of cdk5
activity during drug exposure may limit the ability of an animal to associate
external cues with drug effects, an effect consistent with its blockade of
drug-induced spine formation. Together these findings suggest that the
morphological changes seen following IP amphetamine exposure reflect
associative drug conditioning rather than non-associative drug sensitization. 09/10/2009 |