Impact of regional 5-HT depletion on the cognitive enhancing effects of a typical 5-ht6 receptor antagonist, Ro 04-6790, in the Novel Object Discrimination task

Rationale Selective 5-ht6 receptor antagonists like Ro 04-6790 prolong memory in many rodent preclinical paradigms, possibly by blocking tonic 5-HT-evoked GABA release and allowing disinhibition of cortico-limbic glutamatergic and cholinergic neurones. If this is the case, behavioural responses to Ro 04-6790 should be abolished by depletion of endogenous 5-HT, and selective lesions of dorsal raphe (DR) or median raphe (MR) 5-HT pathways would allow the neuroanatomical substrates underlying the cognitive effects of 5-ht6 receptor antagonists to be elucidated.