Pharmacologic dissociation between impulsivity and alcohol drinking in high alcohol preferring mice.
BACKGROUND
Impulsivity is genetically correlated with, and precedes, addictive behaviors and alcoholism. If impulsivity or attention is causally related to addiction, certain pharmacological manipulations of impulsivity and/or attention may affect alcohol drinking, and vice versa. The current studies were designed to explore the relationship among impulsivity, drinking, and vigilance in selectively bred High Alcohol Preferring (HAP) mice, a line that has previously demonstrated both high impulsivity and high alcohol consumption. Amphetamine, naltrexone, and memantine were tested in a delay discounting (DD) task for their effects on impulsivity and vigilance. The same drugs and doses were also assessed for effects on alcohol drinking in a 2-bottle choice test.


METHODS
HAP mice were subjected to a modified version of adjusting amount DD using 0.5-second and 10-second delays to detect decreases and increases, respectively, in impulsive responding. In 2 experiments, mice were given amphetamine (0.4, 0.8, or 1.2 mg/kg), naltrexone (3 and 10 mg/kg), and memantine (1 and 5 mg/kg) before DD testing. Another pair of studies used scheduled access, 2-bottle choice drinking to assess effects of amphetamine (0.4, 1.2, or 3.0 mg/kg), naltrexone (3 and 10 mg/kg), and memantine (1 and 5 mg/kg) on alcohol consumption.


RESULTS
Amphetamine dose-dependently reduced impulsivity and vigilance decrement in DD, but similar doses left alcohol drinking unaffected. Naltrexone and memantine decreased alcohol intake at doses that did not affect water drinking but had no effects on impulsivity or vigilance decrement in the DD task.


CONCLUSIONS
Contrary to our hypothesis, none of the drugs tested here, while effective on either alcohol drinking or impulsivity, decreased both behaviors. These findings suggest that the genetic association between drinking and impulsivity observed in this population is mediated by mechanisms other than those targeted by the drugs tested in these studies.
Oberlin
Brandon G
BG
Stark Neuroscience Institute, Program in Medical Neuroscience, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Bristow
Robert Evan
RE
Heighton
Meredith E
ME
Grahame
Nicholas J
NJ
D000428:Alcohol Drinking / Q000188:drug therapy / Q000235:genetics / Q000523:psychology*; D000437:Alcoholism / Q000188:drug therapy / Q000235:genetics / Q000523:psychology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy / Q000235:genetics / Q000523:psychology; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007175:Impulsive Behavior / Q000188:drug therapy / Q000235:genetics / Q000523:psychology*; D008297:Male; D008559:Memantine / Q000494:pharmacology; D051379:Mice; D009271:Naltrexone / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D009271:Naltrexone; D000661:Amphetamine; D008559:Memantine