Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: I. Periadolescent exposure.
BACKGROUND
The current study examined the effects of ethanol (EtOH) drinking during periadolescence on the subsequent acquisition and extinction of operant self-administration of EtOH and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats to test the hypothesis that alcohol drinking during periadolescence produces enduring alterations that enhance the reinforcing properties of EtOH.


METHODS
Periadolescent female P rats were given 24 hr free-choice access to 15% (v/v) EtOH starting at postnatal day (PND) 30 and ending on PND 60 or were similarly housed and received water only. On PND 75, without any prior training, periadolescent alcohol-drinking and periadolescent alcohol-naïve rats were placed in standard two-lever (15% EtOH and water) chambers to examine acquisition of EtOH self-administration with a fixed ratio (FR) 1 schedule of reinforcement. After the acquisition phase and after stable responding was established on an FR5 for EtOH and FR1 for water, P rats underwent extinction training for both EtOH and water rewards. After extinction training and a 2 week home cage period, rats were returned to the operant chambers in the absence of reward for seven consecutive sessions (Pavlovian spontaneous recovery). After this testing period, animals were maintained in their home cage for a week before being returned to the operant chambers and allowed to respond for EtOH and water (reacquisition).


RESULTS
Compared with periadolescent alcohol-naïve rats, periadolescent alcohol-drinking rats acquired EtOH responding sooner (i.e., in the first acquisition session), displayed a greater resistance to extinguish EtOH responding (i.e., higher levels of responding in sessions 4-6), had higher responding for more sessions on the EtOH lever in the absence of reward after a prolonged home cage rest period, and had a more prolonged elevated level of EtOH responding during reacquisition (four sessions versus one session).


CONCLUSIONS
Overall, the results suggest that periadolescent EtOH drinking by P rats produced long-lasting alterations in the reinforcing effects of alcohol, which increased the likelihood that alcohol drinking would be initiated in adulthood, decreased the likelihood that once adult alcohol drinking began it could be extinguished easily, and increased the potential for relapse.
Rodd-Henricks
Zachary A
ZA
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis 46202-4887, USA. zrodd@iupui.edu
Bell
Richard L
RL
Kuc
Kelly A
KA
Murphy
James M
JM
McBride
William J
WJ
Lumeng
Lawrence
L
Li
Ting-Kai
TK
D000375:Aging / Q000187:drug effects* / Q000235:genetics; D000428:Alcohol Drinking / Q000235:genetics / Q000523:psychology*; D000818:Animals; D016739:Behavior, Addictive / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D005260:Female; D012646:Self Administration / Q000523:psychology; D013997:Time Factors
D000431:Ethanol