Evaluation of reward processes in an animal model of depression
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.
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.
Materials and 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.
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.
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.
KeywordsAnimal model Reward Depression Antidepressant
- Connor TJ, Harkin A, Kelly JP, Leonard BE (2000) Olfactory bulbectomy provokes a suppression of interleukin-1beta and tumour necrosis factor-alpha production in response to an in vivo challenge with lipopolysaccharide: effect of chronic desipramine treatment. Neuroimmunomodulation 7:27–35PubMedCrossRefGoogle Scholar
- Geyer MA, Markou A (2000) Animal models of psychiatric disorders. In: Watson S (ed) Psychopharmacology: the fourth generation of progress. Lippincott, Williams and Wilkins, PhiladelphiaGoogle Scholar
- Kelly JP, Leonard BE (1993) Dexamethasone suppression of corticosterone secretion in the olfactory bulbectomized rat. Neuropsychopharmacology 9:S137–S138Google Scholar
- Markou A, Koob GF (1993) Intracranial self-stimulation thresholds as a measure of reward. In: Saghal A (ed) Behavioural neuroscience: a practical approach. IRL, Oxford, pp 93–115Google Scholar
- Redmond AM, Kelly JP, Leonard BE (1994) Effect of paroxetine and fluvoxamine on behavioural changes in a number of paradigms in the olfactory bulbectomized rat model of depression. Journal Serotonin Res 1:199–205Google Scholar
- Slattery DA, Markou A, Froestl W, Cryan JF (2005b) The GABAB receptor-positive modulator GS39783 and the GABAB receptor agonist baclofen attenuate the reward-facilitating effects of cocaine: intracranial self-stimulation studies in the rat. Neuropsychopharmacology 30:2065–2072PubMedCrossRefGoogle Scholar