Repeated ethanol exposure and withdrawal impairs human fear conditioning and depresses long-term potentiation in rat amygdala and hippocampus.
BACKGROUND
In rats, repeated episodes of alcohol consumption and withdrawal (RWD) impair fear conditioning to discrete cues.


METHODS
Fear conditioning was measured in human binge drinkers as the increased startle response in the presence of a CS+ conditioned to aversive white noise. Secondly, the ability of tone CSs, paired with footshock, to induce c-fos expression, a marker of neuronal activity, in limbic structures subserving emotion was studied in rats. Additionally, consequences of RWD on subsequent induction of long term potentiation (LTP) in external capsule/lateral amygdala and Schaffer collateral/hippocampus CA1 pathways were studied in rat brain slices.


RESULTS
Fear conditioning was impaired in young human binge drinkers. The ability of fear-conditioned CSs to increase c-fos expression in limbic brain areas was reduced following RWD, as was LTP induction. Rats conditioned prior to RWD, following RWD showed generalization of conditioned fear from the tone CS+ to a neutral control stimulus, and a novel tone.


CONCLUSIONS
Binge-like drinking impairs fear conditioning, reduces LTP, and results in inappropriate generalization of learned fear responses. We propose a mechanism whereby RWD-induced synaptic plasticity reduces capacity for future learning, while allowing unconditioned stimuli access to neuronal pathways underlying conditioned fear.
Stephens
David N
DN
Department of Psychology, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom. d.stephens@sussex.ac.uk
Ripley
Tamzin L
TL
Borlikova
Gilyana
G
Schubert
Manja
M
Albrecht
Doris
D
Hogarth
Lee
L
Duka
Theodora
T
D000328:Adult; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D000431:Ethanol / Q000008:administration & dosage*; D005239:Fear; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013997:Time Factors
D002492:Central Nervous System Depressants; D000431:Ethanol