Ethanol self-administration and reinstatement of ethanol-seeking behavior in Per1(Brdm1) mutant mice.
BACKGROUND
Alcohol consumption shows circadian rhythmicity, i.e., alcohol preference and intake change with circadian time. Circadian rhythmicity is controlled by a biological clock, which has been shown to govern behavioral, physiological, and hormonal processes in synchronization with internal as well as external cues. Molecular components of the clock include circadian clock genes such as period (Per) 1, 2, and 3. Previously, our lab demonstrated the involvement of mouse Per1 (mPer1) and Per2 (mPer2) in modulating cocaine sensitization and reward. What is more, we investigated voluntary alcohol consumption in Per2 ( Brdm1 ) mice with the results suggesting a relationship between this circadian clock gene and ethanol consumption. Objective To further complement the mPer2 study, our lab proceeded to assess mPer1's possible role on alcohol intake using operant and free choice two bottle paradigms.


METHODS
Using operant conditions, Per1 ( Brdm1 ) and wild type mice were trained to self-administer ethanol (10%) under a fixed ratio 1 (FR1) paradigm. This was ensued by a progressive ratio (PR) schedule. Furthermore, extinction sessions were introduced, followed by reinstatement measures of ethanol-seeking behavior. In another set of animals, the mice were exposed to voluntary long-term alcohol consumption, ensued by a 2-month deprivation phase, after which the alcohol deprivation effect (ADE) was measured.


RESULTS
Mutant mice did not display a significantly divergent number of reinforced lever presses (FR1 and PR) than wild type animals. Furthermore, no significant differences between groups were obtained regarding reinstatement of ethanol-seeking behavior. Similar results were obtained in the two bottle free choice paradigm. Specifically, no genotype differences concerning consumption and preference were observed over a broad range of different ethanol concentrations. Moreover, after the deprivation phase, both groups exhibited significant ADEs, yet no genotype differences.


CONCLUSIONS
Contrary to the mPer2 data, the present findings do not suggest a relationship between the circadian clock gene mPer1 and ethanol reinforcement, seeking, and relapse behavior.
Zghoul
Tarek
T
Department of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, J5, 68159, Mannheim, Germany. tarek.zghoul@googlemail.com
Abarca
Carolina
C
Sanchis-Segura
Carles
C
Albrecht
Urs
U
Schumann
Gunter
G
Spanagel
Rainer
R
D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D002755:Choice Behavior / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics*; D003216:Conditioning, Operant / Q000502:physiology; D003433:Crosses, Genetic; D003463:Cues; D005108:Extinction, Psychological / Q000502:physiology; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009042:Motivation; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors