 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, September 1, 2002, 22(17):7687-7694
Metabolic Mapping of the Effects of Cocaine during the Initial Phases of Self-Administration in the Nonhuman Primate
Linda J. Porrino, David Lyons, Mack D. Miller, Hilary R. Smith, David P. Friedman, James B. Daunais, and Michael A. Nader Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157
Because most human studies of the neurobiological substrates of the effects of cocaine have been performed with drug-dependent subjects, little information is available about the effects of cocaine in the initial phases of drug use before neuroadaptations to chronic exposure have developed. The purpose of the present study, therefore, was to define the substrates that mediate the initial effects of cocaine in a nonhuman primate model of cocaine self-administration using the 2-[14C]deoxyglucose method. Rhesus monkeys were trained to self-administer 0.03 mg/kg per injection (N = 4) or 0.3 mg/kg per injection (N = 4) cocaine and compared with monkeys trained to respond under an identical schedule of food reinforcement (N = 4). Monkeys received 30 reinforcers per session, and metabolic mapping was conducted at the end of the fifth self-administration session. Cocaine self-administration reduced glucose utilization in the mesolimbic system, including the ventral tegmental area, ventral striatum, and medial prefrontal cortex. In addition, metabolic activity was increased in the dorsolateral and dorsomedial prefrontal cortex, as well as in the mediodorsal nucleus of the thalamus. These latter effects are distinctly different from those seen after the noncontingent administration of cocaine, suggesting that self-administration engages circuits beyond those engaged merely by the pharmacological actions of cocaine. The involvement of cortical areas subserving working memory suggests that strong associations between cocaine and the internal and external environment are formed from the very outset of cocaine self-administration. The assessment of the effects of cocaine at a time not readily evaluated in humans provides a baseline from which the effects of chronic cocaine exposure can be investigated.
Key words: cocaine; prefrontal cortex; striatum; nucleus accumbens; self-administration; rhesus monkeys
Copyright © 2002 Society for Neuroscience 0270-6474/02/22177687-08$05.00/0
This article has been cited by other articles:
W. K. Schiffer, C. N. B. Liebling, C. Reiszel, J. M. Hooker, J. D. Brodie, and S. L. Dewey
Cue-Induced Dopamine Release Predicts Cocaine Preference: Positron Emission Tomography Studies in Freely Moving Rodents
J. Neurosci., May 13, 2009; 29(19): 6176 - 6185.
[Abstract] [Full Text] [PDF]
C. A. Winstanley, Q. LaPlant, D. E. H. Theobald, T. A. Green, R. K. Bachtell, L. I. Perrotti, R. J. DiLeone, S. J. Russo, W. J. Garth, D. W. Self, et al.
{Delta}FosB Induction in Orbitofrontal Cortex Mediates Tolerance to Cocaine-Induced Cognitive Dysfunction
J. Neurosci., September 26, 2007; 27(39): 10497 - 10507.
[Abstract] [Full Text] [PDF]
M. A. Nader and P. W. Czoty
PET Imaging of Dopamine D2 Receptors in Monkey Models of Cocaine Abuse: Genetic Predisposition Versus Environmental Modulation
Am J Psychiatry, August 1, 2005; 162(8): 1473 - 1482.
[Abstract] [Full Text] [PDF]
Y. Liu, G.-D. Chen, M. R. Lerner, D. J. Brackett, and R. R. Matsumoto
Cocaine Up-Regulates Fra-2 and {sigma}-1 Receptor Gene and Protein Expression in Brain Regions Involved in Addiction and Reward
J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 770 - 779.
[Abstract] [Full Text] [PDF]
N. D. Volkow, G.-J. Wang, Y. Ma, J. S. Fowler, C. Wong, Y.-S. Ding, R. Hitzemann, J. M. Swanson, and P. Kalivas
Activation of Orbital and Medial Prefrontal Cortex by Methylphenidate in Cocaine-Addicted Subjects But Not in Controls: Relevance to Addiction
J. Neurosci., April 13, 2005; 25(15): 3932 - 3939.
[Abstract] [Full Text] [PDF]
D. W. Self, K.-H. Choi, D. Simmons, J. R. Walker, and C. S. Smagula
Extinction Training Regulates Neuroadaptive Responses to Withdrawal from Chronic Cocaine Self-Administration
Learn. Mem., September 1, 2004; 11(5): 648 - 657.
[Abstract] [Full Text] [PDF]
E. Saka, C. Goodrich, P. Harlan, B. K. Madras, and A. M. Graybiel
Repetitive Behaviors in Monkeys Are Linked to Specific Striatal Activation Patterns
J. Neurosci., August 25, 2004; 24(34): 7557 - 7565.
[Abstract] [Full Text] [PDF]
L. J. Porrino, D. Lyons, H. R. Smith, J. B. Daunais, and M. A. Nader
Cocaine Self-Administration Produces a Progressive Involvement of Limbic, Association, and Sensorimotor Striatal Domains
J. Neurosci., April 7, 2004; 24(14): 3554 - 3562.
[Abstract] [Full Text] [PDF]
N. D. Volkow, G.-J. Wang, Y. Ma, J. S. Fowler, W. Zhu, L. Maynard, F. Telang, P. Vaska, Y.-S. Ding, C. Wong, et al.
Expectation Enhances the Regional Brain Metabolic and the Reinforcing Effects of Stimulants in Cocaine Abusers
J. Neurosci., December 10, 2003; 23(36): 11461 - 11468.
[Abstract] [Full Text] [PDF]
S. Ikemoto
Involvement of the Olfactory Tubercle in Cocaine Reward: Intracranial Self-Administration Studies
J. Neurosci., October 15, 2003; 23(28): 9305 - 9311.
[Abstract] [Full Text] [PDF]
D. J. Macey, H. R. Smith, M. A. Nader, and L. J. Porrino
Chronic Cocaine Self-Administration Upregulates the Norepinephrine Transporter and Alters Functional Activity in the Bed Nucleus of the Stria Terminalis of the Rhesus Monkey
J. Neurosci., January 1, 2003; 23(1): 12 - 16.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|