Neuroadaptations of Cdk5 in cholinergic interneurons of the nucleus accumbens and prefrontal cortex of inbred alcohol-preferring rats following voluntary alcohol drinking.
BACKGROUND
Neurobiological studies have identified brain areas and related molecular mechanisms involved in alcohol abuse and dependence. Specific cell types in these brain areas and their role in alcohol-related behaviors, however, have not yet been identified. This study examined the involvement of cholinergic cells in inbred alcohol-preferring rats following 1 month of alcohol drinking. Cyclin-dependent kinase 5 (Cdk5) immunoreactivity (IR), a marker of neuronal plasticity, was examined in cholinergic neurons of the nucleus accumbens (NuAcc) and prefrontal cortex (PFC) and other brain areas implicated in alcohol drinking, using dual immunocytochemical (ICC) procedures. Single Cdk5 IR was also examined in several brain areas implicated in alcohol drinking.


METHODS
The experimental group self-administered alcohol using a 2-bottle-choice test paradigm with unlimited access to 10% (v/v) alcohol and water for 23 h/d for 1 month. An average of 6 g/kg alcohol was consumed daily. Control animals received identical treatment, except that both bottles contained water. Rats were perfused and brain sections were processed for ICC procedures.


RESULTS
Alcohol drinking resulted in a 51% increase in Cdk5 IR cholinergic interneurons in the shell NuAcc, while in the PFC there was a 51% decrease in the percent of Cdk5 IR cholinergic interneurons in the infralimbic region and a 46% decrease in Cdk5 IR cholinergic interneurons in the prelimbic region. Additionally, single Cdk5 IR revealed a 42% increase in the central nucleus of the amygdala (CNA).


CONCLUSIONS
This study identified Cdk5 neuroadaptation in cholinergic interneurons of the NuAcc and PFC and in other neurons of the CNA following 1 month of alcohol drinking. These findings contribute to our understanding of the cellular and molecular basis of alcohol drinking and toward the development of improved region and cell-specific pharmacotherapeutic and behavioral treatment programs for alcohol abuse and alcoholism.
Camp
Marguerite Charlotte
MC
Department of Psychology, The University of Texas at Austin, Austin, Texas 78712, USA.
Mayfield
Roy Dayne
RD
McCracken
Mandy
M
McCracken
Lindsay
L
Alcantara
Adriana Angelica
AA
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000201:enzymology*; D051360:Cyclin-Dependent Kinase 5 / Q000096:biosynthesis* / Q000235:genetics; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D007395:Interneurons / Q000187:drug effects / Q000201:enzymology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; D051360:Cyclin-Dependent Kinase 5