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.