[Abstract Title]. - Society for Neuroscience

Abstract: Background: Dopamine (DA) and the DA D2 receptor (D2R) have been implicated in
obesity as well as drug addiction and are specifically thought to be involved in the rewarding
properties of natural reinforcers (food) and unnatural reinforcers (drug reward) (Volkow and
Wise, 2006). Osborne Mendel (OM) rats are genetically prone to obesity and S5B rats are
genetically resistant to obesity when fed a high fat diet. We have previously shown that normal
ad-libitum fed OM and S5B/P rats do not differ in D2R binding but after given a high-fat diet (35
%) for 6 weeks OM rats showed a 60 % decrease in D2R binding in the striatum compared to
S5B/P rats (Primeaux et al., 2007). Bromocriptine (BC) is a D2R agonist and previous studies
have shown that BC may help in the treatment for both cocaine abuse and obesity (Hoffman,
2007). These effects of BC are thought to be primarily due to its action on central D2R. Based on
our findings of a differential high-fat diet preference and D2R binding profile in these rats, we
hypothesized that OM and S5B/P rats will show a differential preference to cocaine as assessed
by using a conditioned place preference (CPP) procedure. Furthermore, we hypothesize that BC
may differentially affect preference for cocaine in the two strains.
Methods: OM and S5B/P rats were conditioned with cocaine (5 or 10 mg/kg) in one chamber
and saline in the other for 8 days. Rats were then tested for cocaine preference. The time spent in
the cocaine paired chamber was measured after different doses of BC (0.5, 1, 5, 10 & 20 mg/kg)
and vehicle treatments. 4 reconditioning sessions separated each test session. Results: Our results
demonstrated that OM rats showed less of a preference for the cocaine-paired chamber relative to
S5B/P rats. Furthermore, high doses of BC (10mg/kg and 20mg/kg) greatly reduced the
preference for the cocaine-paired chamber in OM rats but only slightly reduced the time S5B rats
spent in the cocaine-paired chamber. Conclusion: Rats that are genetically prone to diet-induced
obesity may be less susceptible to the reinforcing effects of cocaine and more susceptible to a
reduction in the reinforcing effects of cocaine upon treatment with BC. Finally, this study raises
the question of whether people that differ in susceptibility to obesity also differ in susceptibility
to cocaine abuse and our findings suggest that individuals who are resistant to diet-induced
obesity may be more vulnerable to abusing cocaine.
Disclosures: R. Kim, None; J. Cho, None; D. Shustarovich, None; M. Michaelides,
None; B.J. Anderson, None; J.K. Robinson, None; G. Wang, None; S.D. Primeaux,
None; G.A. Bray, None; N.D. Volkow, None; P.K. Thanos, None.
Poster
291. Animal Cognition and Behavior: Learning and Memory: Pharmacology II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 291.27/SS10
Topic: F.02.j. Learning and memory: Pharmacology
Support: NIDA Grant DA017949 TG