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


OBJECTIVE
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.
Romeas
Thomas
T
Department of Pharmacology, University of Montreal, Montreal, Quebec, Canada.
Morissette
Marie-Claude
MC
Mnie-Filali
Ouissame
O
Piñeyro
Graciela
G
Boye
Sandra M
SM
D000661:Amphetamine / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D050882:CREB-Binding Protein / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D004195:Disease Models, Animal; D005518:Food Preferences / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009830:Olfactory Bulb / Q000293:injuries / Q000503:physiopathology; D011803:Quinine / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage
D018712:Analgesics, Non-Narcotic; D000697:Central Nervous System Stimulants; D013549:Sweetening Agents; D013395:Sucrose; D011803:Quinine; D000661:Amphetamine; D050882:CREB-Binding Protein