Simultaneous anhedonia and exaggerated locomotor activation in an animal model of depression

Psychopharmacology (Berl). 2009 Aug;205(2):293-303. doi: 10.1007/s00213-009-1539-y. Epub 2009 Apr 29.


Rationale: Anhedonia, or hyposensitivity to normally pleasurable stimuli, is a cardinal symptom of depression. As such, reward circuitry may comprise a substrate with relevance to this symptom of depression.

Objectives: Our aim was to characterize in the rat changes in the rewarding properties of a pharmacological and a natural stimulus following olfactory bulbectomy (OBX), a pre-clinical animal model of depression.

Methods: We measured amphetamine enhancement of brain stimulation reward, changes in sucrose intake, as well as striatal cAMP response element binding protein (CREB) activity, a molecular index previously associated with depressant-like behavior. Moreover, since alteration of psychomotor activity is also a common symptom of depression, and psychostimulant reward and locomotion are thought to share common neurobiology, we used the same treatment schedule of amphetamine to probe for changes in locomotion.

Results: Our findings show that OBX produces a behavioral phenotype characterized by both anhedonia and exaggerated locomotor activation. Thus, we observed a blunted response to the rewarding properties of amphetamine (1 mg/kg, 21 days post-lesion), a long-lasting reduction in sucrose intake and increased striatal CREB activity. In addition, the same dose of amphetamine, at a coincident time post-lesion, triggered an exaggerated response to its locomotor-stimulant actions.

Conclusions: These paradoxical findings are not consistent with the notion that reward and locomotion are mediated by a common substrate; this dissociation may be useful in modeling psychiatric disorders such as mixed depressive states. In addition, our findings suggest that central reward circuitry may constitute a possible target for rationally designed therapeutics for depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / pharmacology
  • Analgesics, Non-Narcotic / administration & dosage
  • Analysis of Variance
  • Animals
  • Body Weight / drug effects
  • CREB-Binding Protein / metabolism
  • Central Nervous System Stimulants / pharmacology
  • Conditioning, Operant / drug effects
  • Depression / drug therapy
  • Depression / physiopathology*
  • Depression / psychology*
  • Disease Models, Animal
  • Food Preferences / drug effects
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Locomotion / drug effects
  • Locomotion / physiology*
  • Male
  • Olfactory Bulb / injuries
  • Olfactory Bulb / physiopathology
  • Quinine / administration & dosage
  • Rats
  • Rats, Sprague-Dawley
  • Reward*
  • Sucrose / administration & dosage
  • Sweetening Agents / administration & dosage


  • Analgesics, Non-Narcotic
  • Central Nervous System Stimulants
  • Sweetening Agents
  • Sucrose
  • Quinine
  • Amphetamine
  • CREB-Binding Protein