Cocaine and desipramine elicit distinct striatal noradrenergic and behavioral responses in selectively bred obesity-resistant and obesity-prone rats

Behav Brain Res. 2018 Jul 2;346:137-143. doi: 10.1016/j.bbr.2017.11.009. Epub 2017 Nov 9.


Previous studies have demonstrated a role for norepinephrine (NE) in energy regulation and feeding, and basal differences have been observed in hypothalamic NE systems in obesity-prone vs. obesity-resistant rats. Differences in the function of brain reward circuits, including in the nucleus accumbens (NAc), have been shown in obesity-prone vs. obesity-resistant populations, leading many researchers to explore the role of striatal dopamine in obesity. However, alterations in NE transmission also affect NAc mediated behaviors. Therefore, here we examined differences in striatal NE and the response to norepinephrine transporter blockers in obesity-prone and obesity-resistant rats. We found that striatal NE levels increase following systemic cocaine administration in obesity-prone, but not obesity-resistant rats. This could result from either blockade of striatal norepinephrine transporters (NET) by cocaine leading to reduced NE reuptake, or circuit-based responses following cocaine administration resulting in increased NE release. Retrodialysis of the NET inhibitor, desipramine, into the ventral striatum did not cause selective increases in striatal NE levels in obesity-prone rats, suggesting that circuit-based mechanisms underlie NE increases following systemic cocaine administration. Consistent with this, systemic desipramine treatment decreased locomotor activity in obesity-prone, but not obesity-resistant rats. Furthermore, obesity-prone rats were also more sensitive to desipramine-induced reductions in food intake compared to obesity-resistant rats. Taken together, these data expand our understanding of differences in NE systems of obesity-prone vs. resistant rats, and provide new insights into basal differences in striatal systems that may influence feeding behavior.

Keywords: Diet induced obesity; Food intake; Microdialysis; Norepinephrine; Norepinephrine transporter; Striatum.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Central Nervous System Agents / pharmacology*
  • Cocaine / pharmacology*
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Desipramine / pharmacology*
  • Dopamine / metabolism
  • Eating / drug effects
  • Eating / physiology
  • Genetic Predisposition to Disease
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Norepinephrine / metabolism*
  • Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism
  • Obesity / genetics
  • Obesity / physiopathology*
  • Rats
  • Serotonin / metabolism
  • Species Specificity


  • Central Nervous System Agents
  • Norepinephrine Plasma Membrane Transport Proteins
  • Serotonin
  • Cocaine
  • Desipramine
  • Dopamine
  • Norepinephrine