The 5-HT7 receptor: Role in novel object discrimination and relation to novelty-seeking behavior

Abstract

Despite showing high affinity for neuroleptics and hallucinogens, the function of the 5-HT7 receptor in cognition remains largely speculative. This study tests the hypothesis that 5-HT7 participates in gauging salience of novel visual stimuli as a function of the animal’s initial tendency for novelty-seeking. Novelty-seeking behavior in the rat is thought to model some aspects of sensation-seeking in humans, a personality trait closely associated to drug abuse. We analyzed the effects of the 5-HT7 receptor antagonist SB269.970 (3 mg kg −1 or 15 mg kg −1 i.p.) on object-recognition tasks using rats that differed in exploration of novel environments, namely high (HR) and low (LR) responders. The task involved a first encounter with an object (“old”), which after a delay of 3 h had to be discriminated from a different object (“new”). The antagonist was injected into HR and LR rats immediately after the first encounter with the objects and its effects on recall of objects were evaluated. In the absence of drug, LR but not HR rats were able to discriminate the familiarity of previously encountered objects. A low dose (3 mg kg −1) of SB269.970 was ineffective in altering object discrimination. A higher dose (15 mg kg −1) inhibited novel-object exploration in LR animals thus curtailing differences in object recognition, a finding that was replicated. In order to validate our studies, the effects of the cholinergic muscarinic antagonist scopolamine (0.2 mg kg −1, i.p.) on object recognition were also evaluated in one of the cohorts 2 weeks after the first NOD experiment. In the Choice phase, all vehicle-treated rats succeeded in recognizing the new object. Scopolamine inhibited object discrimination in HR rats more efficiently than it did in LR rats. Taken together, these results suggest that 5-HT7 may mediate attentional and memory processes relevant to novelty-induced arousal.