Relapse to cocaine-seeking after hippocampal theta burst stimulation.
Treatment efforts for cocaine addiction are hampered by high relapse rates. To map brain areas underlying relapse, we used electrical brain stimulation and intracranial injection of pharmacological compounds after extinction of cocaine self-administration behavior in rats. Electrical stimulation of the hippocampus containing glutamatergic fibers, but not the medial forebrain bundle containing dopaminergic fibers, elicited cocaine-seeking behavior dependent on glutamate in the ventral tegmental area. This suggests a role for glutamatergic neurotransmission in relapse to cocaine abuse. The medial forebrain bundle electrodes supported intense electrical self-stimulation. These findings suggest a dissociation of neural systems subserving positive reinforcement (self-stimulation) and incentive motivation (relapse).
Vorel
S R
SR
Department of Neuroscience, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA. robvorel@hotmail.com
Liu
X
X
Hayes
R J
RJ
Spector
J A
JA
Gardner
E L
EL
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000517:prevention & control; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D004558:Electric Stimulation; D004566:Electrodes; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007275:Injections, Intravenous; D007736:Kynurenic Acid / Q000494:pharmacology; D008474:Medial Forebrain Bundle / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012008:Recurrence; D012201:Reward; D012646:Self Administration; D009435:Synaptic Transmission / Q000187:drug effects; D013826:Theta Rhythm; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016202:N-Methylaspartate; D007736:Kynurenic Acid; D003042:Cocaine; D004298:Dopamine