Elsevier

Neuroscience

Volume 159, Issue 4, 10 April 2009, Pages 1193-1199
Neuroscience

Behavioural Neuroscience
Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity

https://doi.org/10.1016/j.neuroscience.2009.02.007Get rights and content

Abstract

Increased caloric intake in dietary obesity could be driven by central mechanisms that regulate reward-seeking behavior. The mesolimbic dopamine system, and the nucleus accumbens in particular, underlies both food and drug reward. We investigated whether rat dietary obesity is linked to changes in dopaminergic neurotransmission in that region. Sprague–Dawley rats were placed on a cafeteria-style diet to induce obesity or a laboratory chow diet to maintain normal weight gain. Extracellular dopamine levels were measured by in vivo microdialysis. Electrically evoked dopamine release was measured ex vivo in coronal slices of the nucleus accumbens and the dorsal striatum using real-time carbon fiber amperometry. Over 15 weeks, cafeteria-diet fed rats became obese (>20% increase in body weight) and exhibited lower extracellular accumbens dopamine levels than normal weight rats (0.007±0.001 vs. 0.023±0.002 pmol/sample; P<0.05). Dopamine release in the nucleus accumbens of obese rats was stimulated by a cafeteria-diet challenge, but it remained unresponsive to a laboratory chow meal. Administration of d-amphetamine (1.5 mg/kg i.p.) also revealed an attenuated dopamine response in obese rats. Experiments measuring electrically evoked dopamine signal ex vivo in nucleus accumbens slices showed a much weaker response in obese animals (12 vs. 25×106 dopamine molecules per stimulation, P<0.05). The results demonstrate that deficits in mesolimbic dopamine neurotransmission are linked to dietary obesity. Depressed dopamine release may lead obese animals to compensate by eating palatable “comfort” food, a stimulus that released dopamine when laboratory chow failed.

Section snippets

Animals

Female albino Sprague–Dawley rats (Taconic, Hudson, NY, USA), were matched for a body weight of 300 g each at the age of 3 months. Female animals were chosen because, in contrast to male rats, the body weight of laboratory-chow fed females is relatively stable over time. Animals were housed individually in the same room under a 12-h reverse light/dark cycle (lights on: 6 pm, lights off: 6 am). Under these conditions we observed no impact of the estrous cycle phase on mesolimbic dopamine release

Dietary obese rats have a strong preference for highly palatable food

Cafeteria DIO rats showed a strong preference for sweet milk (74.4±6.4 g; 241±21 kcal) and the 32% sucrose solution (31.4±4.1 g; 40±5 kcal) (Fig. 1A, B,F(9,127)=116.9854, P<0.01). In addition, these animals ate significantly less of the Purina chow (5.66±1.02 g) compared to the laboratory chow fed animals (54.7±2.3 g; F(1,27)=419.681, P<0.01). After 14 weeks on the cafeteria diet, rats gained 53.7% of their initial body weight to a final weight of 444.9±19.0 g. After the same period, rats on

Discussion

In this study, rats became overweight from eating a cafeteria diet with a preference for high-carbohydrate foods. In their overweight state, they had lower basal extracellular dopamine as well as chow-stimulated or amphetamine-stimulated dopamine in the nucleus accumbens. In studies using drugs of abuse, animals will work to keep dopamine levels in the nucleus accumbens above a certain level (Wise et al 1995a, Wise et al 1995b, Ranaldi et al 1999). In the present study, the abused “substance”

Conclusion

In conclusion, the findings in this study show that the mesolimbic dopamine system plays a critical role in preference for high-energy diets, hyperphagia and the resulting dietary obesity. The nucleus accumbens and dorsal striatum dopaminergic neurotransmission are depressed in dietary obese rats. The animals can temporarily restore dopamine levels by eating highly palatable, high-energy food. These results suggest that selective targeting of presynaptic regulators of the mesolimbic dopamine

Acknowledgments

This work was supported by DK065872 (ENP), F31 DA023760 (BMG, ENP), a Smith Family Foundation Award of Excellence in Biomedical Research (ENP) and P30 NS047243 (Tufts Center for Neuroscience Research).

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