Insulin resistant rats display enhanced rewarding effects of nicotine.
BACKGROUND
Tobacco use among persons with Type II diabetes exponentially increases negative health consequences and mortality rates. It is especially troubling that diabetic persons who smoke have a greater difficulty with tobacco cessation as compared to non-diabetic smokers. Diabetes is a metabolic syndrome that consists of insulin resistance due to disruptions in insulin signaling. We have previously shown that insulin depletion enhances the motivational effects of nicotine.


METHODS
The present study expands our previous work by examining whether insulin resistance, produced by a high-fat diet (HFD) regimen, enhances the rewarding effects of nicotine, as measured by the conditioned place preference (CPP) paradigm. Rats were placed on either a regular diet (RD) or a HFD for 5 weeks, after which they were assessed for insulin resistance via blood glucose measurements after an insulin challenge. Rats then underwent a nicotine CPP study.


RESULTS
The findings revealed that HFD produced insulin resistant and non-insulin resistant animals. Interestingly, the magnitude of nicotine CPP was larger in insulin resistant rats versus RD rats. Nicotine CPP was absent in non-insulin resistant animals. A similar increase in body weight was observed in insulin resistant and non-insulin resistant rats as compared to RD rats. These findings suggest that neither the increased body weight nor the HFD per se in the insulin resistant rats contributed to the enhanced nicotine reward.


CONCLUSIONS
These present study suggests that insulin resistant rats undergo unique neurobiological changes related to a disruption in insulin signaling that promotes the rewarding effects of nicotine.
Department of Pharmaceutical Sciences, Western University of Health Sciences, 309 East Second Street, Pomona, CA 91766, United States.
Janell R
JR
Richardson
Department of Psychology, University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968, United States.
Joseph A
JA
Pipkin
Department of Psychology, University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968, United States.
Laura E
LE
O'Dell
Department of Pharmaceutical Sciences, Western University of Health Sciences, 309 East Second Street, Pomona, CA 91766, United States. Electronic address: anazarian@westernu.edu.
Arbi
A
Nazarian
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003216:Conditioning, Operant; D003463:Cues; D004032:Diet; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
D001786:Blood Glucose; D018722:Nicotinic Agonists; D009538:Nicotine
Conditioned place preference; Diabetes; Drug use; High fat diet; Insulin resistance; Tobacco