LTP in the lateral amygdala during cocaine withdrawal.
The amygdala plays key roles in several aspects of addiction to drugs of abuse. This brain structure has been implicated in behaviours that reflect drug reward, drug seeking, and the aversive effects of drug withdrawal. Using a model that involves repeated cocaine injections to approximate 'binge' intoxication, we show in rats that during cocaine withdrawal, the impact of rewarding brain stimulation is attenuated, as quantified by alterations in intracranial self-stimulation (ICSS) behaviour. These behavioural signs of withdrawal are accompanied by enhancements of glutamatergic synaptic transmission within the lateral amygdala (LA) that occlude electrically induced long-term potentiation (LTP) in tissue slices. Synaptic enhancements during periods of cocaine withdrawal are mechanistically similar to LTP induced with electrical stimulation in control slices, as both forms of synaptic plasticity involve an increase in glutamate release. These results suggest that mechanisms of LTP within the amygdala are recruited during withdrawal from repeated exposure to cocaine. As such, they raise the possibility that the development and maintenance of addictive behaviours may involve, at least in part, mechanisms of synaptic plasticity within specific amygdala circuits.
Goussakov
Ivan
I
Department of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, Massachusetts 02478, USA.
Chartoff
Elena H
EH
Tsvetkov
Evgeny
E
Gerety
Lyle P
LP
Meloni
Edward G
EG
Carlezon
William A
WA
Bolshakov
Vadim Y
VY
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000008:administration & dosage*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005239:Fear; D018755:GABA Agonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D009118:Muscimol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D003042:Cocaine