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. 2014 Jul 1:140:205-7.
doi: 10.1016/j.drugalcdep.2014.03.028. Epub 2014 Apr 5.

Insulin resistant rats display enhanced rewarding effects of nicotine

Janell R Richardson  1 , Joseph A Pipkin  2 , Laura E O'Dell  2 , Arbi Nazarian  3
Affiliations

Insulin resistant rats display enhanced rewarding effects of nicotine

Janell R Richardson et al. Drug Alcohol Depend. .

Abstract

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.

Conclusion: 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.

Keywords: Conditioned place preference; Diabetes; Drug use; High fat diet; Insulin resistance; Tobacco.

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Conflict of interest statement

Conflict of interest

The authors have no relevant conflicts of interest to disclose.

Figures

Fig. 1.
Fig. 1.
Mean (±S.E.M) blood glucose levels and body weight in HFD and RD treated rats. Panel A: Plasma blood glucose levels were measured prior to and at timed intervals following an injection of insulin (0.75 U/kg, i.p.). Panel B: Fasting body weights (g) taken just prior to the insulin challenge. n = 8–12 rats/group. *Represents differences from RD control group (p < 0.05).
Fig. 2.
Fig. 2.
Mean (±S.E.M) difference in time spent (s) in the drug-paired chamber between preconditioning and postconditioning test days for rats conditioned with saline or nicotine (0.2 mg/kg) in the CPP paradigm. HFD insulin resistant rats exhibited greater rewarding effects of nicotine as compared to RD controls, whereas HFD non-insulin resistant rats did not exhibit any rewarding effects of nicotine. n = 6–9 rats/group. *Represents differences between indicated groups (p < 0.05).
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References

    1. Ahren B, Gudbjartsson T, Al-Amin AN,Martensson H,Myrsen-Axcrona U, Karlsson S, Mulder H, Sundler F, 1999. Islet perturbations in rats fed a high-fat diet. Pancreas 18, 75–83. - PubMed
    1. Baladi MG, Newman AH, France CP, 2011. Influence of body weight and type of chow on the sensitivity of rats to the behavioral effects of the direct-acting dopamine-receptor agonist quinpirole. Psychopharmacology (Berl.) 217, 573–585. - PMC - PubMed
    1. Blendy JA, Strasser A, Walters CL, Perkins KA, Patterson F, Berkowitz R, Lerman C, 2005. Reduced nicotine reward in obesity: cross-comparison in human and mouse. Psychopharmacology (Berl.) 180, 306–315. - PubMed
    1. Buettner R, Parhofer KG, Woenckhaus M, Wrede CE, Kunz-Schughart LA, Scholmerich J, Bollheimer LC, 2006. Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. J. Mol. Endocrinol. 36, 485–501. - PubMed
    1. Buse JB, Bigger JT, Byington RP, Cooper LS, Cushman WC, Friedewald WT, Genuth S, Gerstein HC, Ginsberg HN, Goff DC Jr., Grimm RH Jr., Margolis KL, Probstfield JL, Simons-Morton DG, Sullivan MD, 2007. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am. J. Cardiol. 99, 21i–33i. - PubMed

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