Intracranial self-administration of cocaine within the posterior ventral tegmental area of Wistar rats: evidence for involvement of serotonin-3 receptors and dopamine neurons.
The rewarding properties of cocaine have been postulated to be regulated, in part, by the mesolimbic dopamine (DA) system. The present study assessed whether adult female Wistar rats would self-administer cocaine directly into the ventral tegmental area (VTA). Following guide cannulae surgery aimed at either the posterior or anterior VTA, subjects were placed in an operant box equipped with an active lever that caused the delivery of the infusate and an inactive lever that did not. Posterior and anterior VTA subjects were randomly assigned to one of six groups that self-administered either artificial cerebrospinal fluid (aCSF) or 25 to 400 pmol cocaine/100 nl in aCSF for the first four sessions, aCSF in sessions 5 and 6, and the acquisition dose of infusate during session 7. Additionally, the effects of increasing the time-out period, higher concentrations of cocaine, coadministration of a 5HT3 antagonist, and coadministration of a D2/3 agonist on self-infusion of cocaine were determined. Self-infusions were maintained when the time-out period was extended from 5 to 25 s. Coinfusion of a 5HT3 antagonist or D2/3 agonist blocked the self-infusion of cocaine. In contrast, rats did not self-administer 25 to 400 pmol/100 nl cocaine into the anterior VTA. Additionally, rats did not self-administer either 800 or 1600 pmol/100 nl cocaine into the posterior or anterior VTA. Overall, the data indicate that the VTA is functionally heterogeneous with regard to the rewarding actions of cocaine and that the reinforcing effects of cocaine within the posterior VTA are mediated by activation 5-HT3 receptors and DA neurons.
Rodd
Zachary A
ZA
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA. zrodd@iupui.edu
Bell
Richard L
RL
Kuc
Kelly A
KA
Zhang
Ying
Y
Murphy
James M
JM
McBride
William J
WJ
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007267:Injections; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects*; D012646:Self Administration; D000077526:Tropisetron; D017557:Ventral Tegmental Area
D018491:Dopamine Agonists; D007211:Indoles; D044406:Receptors, Serotonin, 5-HT3; D019257:Quinpirole; D000077526:Tropisetron; D003042:Cocaine; D004298:Dopamine