The clinical course of cocaine abuse has been characterized as progressing through a number of temporal stages that advance from initial experimentation to addiction. This clinical course is paralleled by changes in the neurobiological response to cocaine, as well as residual changes in function and structure that can persist despite periods of abstinence. During the past finding period we have employed a non-human primate model of cocaine self-administration to map the constellation of cerebral metabolic changes associated with the initial phases of self-administration and compared these effects to those that occur following chronic exposure (3.3 months). In addition, we have characterized the topography of changes in markers of the dopamine system that result from continued cocaine self administration. Increasing durations of cocaine exposure produced an intensification and widening of metabolic and structural changes across functional domains in the non-human primate brain. This change in functional topography suggests a marked change in the response to cocaine as a consequence of duration drug history. Given this, two questions arise. First, is there a continued progression of change in structure and function with increasing durations of self-administration history? Second, is there a reversal of topographic alterations following cessation of drug taking? In the present proposal the functional effects of 1.5 years of cocaine self-administration will be assessed. In addition, the effects of abstinence (1 and 3 months) following moderate and prolonged periods of self-administration on these functional markers will be measured. Identifying these changes will provide the basis for clearer evaluations of treatment strategies whether pharmacological or behavioral.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (04))
Program Officer
Pilotte, Nancy S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Wake Forest University Health Sciences
Schools of Medicine
United States
Zip Code
Porrino, Linda J; Beveridge, Thomas J R; Smith, Hilary R et al. (2016) Functional consequences of cocaine expectation: findings in a non-human primate model of cocaine self-administration. Addict Biol 21:519-29
Porrino, Linda J; Miller, Mack D; Smith, Hilary R et al. (2016) Neural Correlates of Exposure to Cocaine Cues in Rhesus Monkeys: Modulation by the Dopamine Transporter. Biol Psychiatry 80:702-710
Smith, Hilary R; Beveridge, Thomas J R; Nader, Michael A et al. (2014) Regionally-specific alterations in myelin proteins in nonhuman primate white matter following prolonged cocaine self-administration. Drug Alcohol Depend 137:143-7
Beveridge, Thomas J R; Smith, Hilary R; Nader, Susan H et al. (2014) Functional consequences of cocaine re-exposure after discontinuation of cocaine availability. Neuropharmacology 85:528-37
Calipari, Erin S; Beveridge, Thomas J R; Jones, Sara R et al. (2013) Withdrawal from extended-access cocaine self-administration results in dysregulated functional activity and altered locomotor activity in rats. Eur J Neurosci 38:3749-57
Hanlon, Colleen A; Beveridge, Thomas J R; Porrino, Linda J (2013) Recovering from cocaine: insights from clinical and preclinical investigations. Neurosci Biobehav Rev 37:2037-46
Gould, Robert W; Porrino, Linda J; Nader, Michael A (2012) Nonhuman primate models of addiction and PET imaging: dopamine system dysregulation. Curr Top Behav Neurosci 11:25-44
Taber, Katherine H; Black, Deborah N; Porrino, Linda J et al. (2012) Neuroanatomy of dopamine: reward and addiction. J Neuropsychiatry Clin Neurosci 24:1-4
Beveridge, T J R; Smith, H R; Nader, M A et al. (2011) Group II metabotropic glutamate receptors in the striatum of non-human primates: dysregulation following chronic cocaine self-administration. Neurosci Lett 496:15-9
Hampson, R E; EspaƱa, R A; Rogers, G A et al. (2009) Mechanisms underlying cognitive enhancement and reversal of cognitive deficits in nonhuman primates by the ampakine CX717. Psychopharmacology (Berl) 202:355-69

Showing the most recent 10 out of 36 publications