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D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell.

Publication ,  Journal Article
Kalyanasundar, B; Perez, CI; Luna, A; Solorio, J; Moreno, MG; Elias, D; Simon, SA; Gutierrez, R
Published in: J Neurophysiol
July 2015

Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds.

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Published In

J Neurophysiol

DOI

EISSN

1522-1598

Publication Date

July 2015

Volume

114

Issue

1

Start / End Page

585 / 607

Location

United States

Related Subject Headings

  • Weight Loss
  • Stereotyped Behavior
  • Sleep Initiation and Maintenance Disorders
  • Receptors, Dopamine D2
  • Receptors, Dopamine D1
  • Rats, Sprague-Dawley
  • Random Allocation
  • Raclopride
  • Phentermine
  • Nucleus Accumbens
 

Citation

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Kalyanasundar, B., Perez, C. I., Luna, A., Solorio, J., Moreno, M. G., Elias, D., … Gutierrez, R. (2015). D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell. J Neurophysiol, 114(1), 585–607. https://doi.org/10.1152/jn.00012.2015
Kalyanasundar, B., Claudia I. Perez, Alvaro Luna, Jessica Solorio, Mario G. Moreno, David Elias, Sidney A. Simon, and Ranier Gutierrez. “D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell.J Neurophysiol 114, no. 1 (July 2015): 585–607. https://doi.org/10.1152/jn.00012.2015.
Kalyanasundar B, Perez CI, Luna A, Solorio J, Moreno MG, Elias D, et al. D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell. J Neurophysiol. 2015 Jul;114(1):585–607.
Kalyanasundar, B., et al. “D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell.J Neurophysiol, vol. 114, no. 1, July 2015, pp. 585–607. Pubmed, doi:10.1152/jn.00012.2015.
Kalyanasundar B, Perez CI, Luna A, Solorio J, Moreno MG, Elias D, Simon SA, Gutierrez R. D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell. J Neurophysiol. 2015 Jul;114(1):585–607.

Published In

J Neurophysiol

DOI

EISSN

1522-1598

Publication Date

July 2015

Volume

114

Issue

1

Start / End Page

585 / 607

Location

United States

Related Subject Headings

  • Weight Loss
  • Stereotyped Behavior
  • Sleep Initiation and Maintenance Disorders
  • Receptors, Dopamine D2
  • Receptors, Dopamine D1
  • Rats, Sprague-Dawley
  • Random Allocation
  • Raclopride
  • Phentermine
  • Nucleus Accumbens