Evaluation of reward processes in an animal model of depression.
BACKGROUND
Anhedonia is a core symptom of major depression. Deficits in reward function, which underlie anhedonia, can be readily assessed in animals. Therefore, anhedonia may serve as an endophenotype for understanding the neural circuitry and molecular pathways underlying depression.


OBJECTIVE
Surprisingly, there is scant knowledge regarding alterations in brain reward function after olfactory bulbectomy (OB), an animal model which results in a behavioural syndrome responsive to chronic antidepressant treatment. Therefore, the present studies aimed to assess reward function after bulbectomy.


METHODS
The present study utilized sucrose preference, cocaine-induced hyperlocomotion and intra-cranial self-stimulation (ICSS) responding to examine reward processes in the OB model.


RESULTS
Bulbectomized animals showed a marked preference (>90%) for 0.8% sucrose solution compared with water; similar to the preference exhibited by sham controls. Importantly, there were pronounced deficits in brain reward function, as assessed using ICSS, which lasted 8 days before returning to baseline levels. Furthermore, bulbectomized animals were hyper-responsive to the locomotor stimulating properties of an acute and a repeated cocaine regimen. However, no difference in ICSS facilitation was observed in response to an acute cocaine injection.


CONCLUSIONS
Taken together, these results suggest that bulbectomized rats display alterations in brain reward function, but these changes are not long-lasting and thus, not amenable to investigating the effects of pharmacological interventions. However, given that OB animals are hypersensitive to drugs of abuse, bulbectomy may be an appropriate inducing factor for the development of animal models of co-morbid depression and drug dependence.
Slattery
David A
DA
Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Markou
Athina
A
Cryan
John F
JF
D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D003042:Cocaine / Q000008:administration & dosage; D003863:Depression / Q000523:psychology*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009830:Olfactory Bulb / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects; D012684:Sensory Thresholds; D013395:Sucrose; D013997:Time Factors
D000697:Central Nervous System Stimulants; D013395:Sucrose; D003042:Cocaine