Long-term development of excessive and inflexible nicotine taking by rats, effects of a novel treatment approach.
BACKGROUND
Addiction is characterized by inflexible drug consumption: unpleasant consequences are accepted. Rat studies with several drugs proved that long-term voluntary intake induced abstinence-outlasting excessive and inflexible consumption.


OBJECTIVE
Establishing a long-term model of oral self-administration of nicotine in rats with outlasting consequences for flexibility; testing a novel approach to restore flexibility by increasing neuroplasticity for memory reorganization via glucocorticoids.


METHODS
2 test groups of male Wistar rats were given continuous free choice between water and 8, 16, 32mg/l nicotine solutions for 48 weeks. Two other groups received water or 4mg/l nicotine as sole drinking fluid. After 10 weeks abstinence, all rats were given nicotine choice in a retest. Nicotine solutions were then adulterated with bitter-tasting quinine to test flexibility. In two treatment sessions (3 weeks, each), half of the rats received placebo, the other ones 250mg/l corticosterone, corticosterone plus 4mg/l nicotine and finally 4mg/l nicotine (1 week per phase).


RESULTS
Voluntary intake groups developed a flexible, moderate consumption revealed by reversible influences of social conditions. Intake was individually stable but varied among subjects. In the retest, all rats from water and forced groups showed moderate, flexible intake whereas several rats from the choice groups were excessive, inflexible consumers. The treatment was effective in selectively reducing inflexible, excessive consumption.


CONCLUSIONS
Long-term voluntary intake of nicotine, but not forced one, induces abstinence-enduring loss of flexibility in part of the rats. The tested treatment approach seems suitable to degrade an established addiction memory in rats.
Galli
Gabriel
G
Medimod Research Institute GmbH, Germany. Gabriel.galli@curamentis.com
Wolffgramm
Jochen
J
D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects*; D003345:Corticosterone / Q000008:administration & dosage; D004195:Disease Models, Animal; D004327:Drinking Behavior / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*
D018722:Nicotinic Agonists; D009538:Nicotine; D003345:Corticosterone