The P/NP and HAD1-2/LAD1-2 rat lines and the HAP1-2-3/LAP2-3 and cHAP mouse lines have been selectively bred for opposite alcohol preference and are maintained by the APC. They are the best characterized extant heritable rodent models for studying factors that influence the development of alcoholism;e.g., the CNS reward circuitry, the relationship of temperament to alcohol preference, and the consequences of excessive drinking in these rodents that include "binge" drinking, the alcohol-deprivation effect ("relapse" and "out-of-control" drinking), and peri-adolescent alcohol abuse. The P and HAD1 rats are being used to test novel proprietary molecules that can curtail alcohol drinking in an NIAAA-HHSN Contract. New data also indicate that the P rats can serve as an invaluable model to investigate the science/genetics of addiction, i.e. co-abuse of alcohol and other substances. Recent data further indicate that the HAP1 and cHAP mice routinely exhibit blood alcohol concentrations that exceed 200mg% during free-choice alcohol drinking.
The Specific Aims (SAs) include- SA1: To maintain our nucleus colonies of selectively bred P/NP rats and inbred strains (iPlOa and INPI) and to supply sufficient number of these and HAD1-2/LAD1-2 rats to on-campus researchers. SA2: To continue to selectively breed the replicate HAP/LAP mouse lines and the cHAP line as nucleus colonies and to produce these animal subjects for on-campus researchers. SAS: To continue to maintain two congenics, iNP.IP and IP.INP, in which IP rat chr 4 QTL was transferred to the iNP and vice versa and one interval specific congenic strain (ISCS). SA4: To actively participate in one Research Component and two Pilot Projects in this ARC renewal. This APC is the cornerstone of a number of NlAAAfunded grants: four ROIs, one R24, two INIA-West Projects, one T32 Training grant, and one NIAAA-HHSN Contract. Among the pending NIAAA grants, we anticipate that many of them will get funded, and if our P60 ARC is re-newed, the APC will actively support three new Research Components and three Pilot Projects. We expect that by way of the afore-cited SAs and providing research subjects for all the afore-mentioned NlAAA-funded grants, this APC will help to pave the way to groundbreaking discoveries.
Co-abuse of alcohol and other addictive substances is a rampant public health problem that involves many genes and pathways interacting with environmental factors by epigenetic and other mechanisms. P rats, a genetic rodent model, will work by bar-pressing to obtain alcohol and nicotine, and pharmacologic studies indicate that this behavior is mediated by nicotine and marijuana receptors in the brain. These studies iand others indicate that P rats will be extremely useful to elucidate the genetics and science of addiction.
|Wardell, Jeffrey D; Ramchandani, Vijay A; Hendershot, Christian S (2016) Drinking Motives Predict Subjective Effects of Alcohol and Alcohol Wanting and Liking During Laboratory Alcohol Administration: A Mediated Pathway Analysis. Alcohol Clin Exp Res 40:2190-2198|
|McClintick, Jeanette N; McBride, William J; Bell, Richard L et al. (2016) Gene Expression Changes in Glutamate and GABA-A Receptors, Neuropeptides, Ion Channels, and Cholesterol Synthesis in the Periaqueductal Gray Following Binge-Like Alcohol Drinking by Adolescent Alcohol-Preferring (P) Rats. Alcohol Clin Exp Res 40:955-68|
|Yoder, Karmen K; Albrecht, Daniel S; Dzemidzic, Mario et al. (2016) Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics. Drug Alcohol Depend 160:163-9|
|Bell, R L; Hauser, S; Rodd, Z A et al. (2016) A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction. Int Rev Neurobiol 126:179-261|
|Sari, Youssef; Toalston, Jamie E; Rao, P S S et al. (2016) Effects of ceftriaxone on ethanol, nicotine or sucrose intake by alcohol-preferring (P) rats and its association with GLT-1 expression. Neuroscience 326:117-25|
|Ding, Zheng-Ming; Ingraham, Cynthia M; Rodd, Zachary A et al. (2016) Alcohol drinking increases the dopamine-stimulating effects of ethanol and reduces D2 auto-receptor and group II metabotropic glutamate receptor function within the posterior ventral tegmental area of alcohol preferring (P) rats. Neuropharmacology 109:41-8|
|O'Tousa, David S; Grahame, Nicholas J (2016) Long-Term Alcohol Drinking Reduces the Efficacy of Forced Abstinence and Conditioned Taste Aversion in Crossed High-Alcohol-Preferring Mice. Alcohol Clin Exp Res 40:1577-85|
|King, Andrea C; Hasin, Deborah; O'Connor, Sean J et al. (2016) A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder. Biol Psychiatry 79:489-98|
|Beckwith, Steven Wesley; Czachowski, Cristine Lynn (2016) Alcohol-Preferring P Rats Exhibit Elevated Motor Impulsivity Concomitant with Operant Responding andÂ Self-Administration of Alcohol. Alcohol Clin Exp Res 40:1100-10|
|Qiu, Bin; Bell, Richard L; Cao, Yong et al. (2016) Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight. J Genet Genomics 43:421-30|
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