During the present reporting period, our research in this area was limited due to severe reductions in available research resources. Nevertheless, we carried out two research projects. The first involved the use of aggregated single-walled carbon nanotubes and the behavioral and neurochemical effects of methamphetamine in mice. We found that aggregated single-walled carbon nanotubes significantly inhibited methamphetamine self-administration, methamphetamine-induced conditioned place preference, and methamphetamine- or cue-induced relapse to drug-seeking behavior in mice. The administration of single-walled carbon nanotubes did not by themselves alter the mesolimbic dopamine system, but pre-treatment with single-walled carbon nanotubes attenuated methamphetamine-induced increases in extracellular dopamine in the ventral striatum. Electrochemical measurements suggested that single-walled carbon nanotubes facilitate dopamine oxidation. In addition, single-walled carbon nanotubes significantly attenuated methamphetamine-induced increases in tyrosine hydroxylase and in synaptic protein expression. We additionally studied intravenous cocaine self-administration in laboratory rats, combined with in vivo measurements of dopamine in the nucleus accumbens in an attempt to distinguish between dopamine surfeit and deficit as they relate to cocaine self-administration. Dopamine's role in drug self-administration has been much debated - with three main competing explanatory rubrics - hedonic impact (liking), reward prediction, and incentive salience (wanting). In the cocaine self-administration paradigm, acute cocaine produces dopamine surfeit in the ventral neostriatum, whereas chronic self-administration produces dopamine deficit and decreased phasic dopamine signaling in the neostriatum. However, these effects are importantly dependent upon the exact medial-lateral placement of the dopamine detection in the neostriatum. We conclude that the relationship between neostriatal dopaminergic dynamics and drug-taking is more complex than hitherto realized.
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