Abstract
Activation of 5-hydroxytyptamine6 (5-HT6) receptors stimulates attentional switching and 5-HT6 receptor antagonists are putative drugs for psychosis. Latent inhibition (LI) provides a pre-clinical model of attentional switching and ‘antipsychotic-like’ action and is known to be modulated by 5-hydroxytyptamine. In the present study, LI was shown in a fear conditioning procedure that measured suppression of drinking after conditioning with footshock. In two experiments (each n = 48) it was shown that pre-exposure to both light- and noise-conditioned stimuli reduced conditioned suppression relative to the corresponding non-pre-exposed control. However, counter to prediction, LI was intact after treatment with the 5-HT6 agonist EMD386088 (5 mg/kg).
Highlights
Amongst the multiplicity of 5-hydroxytyptamine receptor subtypes, the 5-hydroxytyptamine6 (5-HT6) receptor in particular is located in brain regions involved in learning and memory (Fone, 2008; Ivachtchenko et al, 2016)
The baseline licking scores seen preconditioning confirmed that the rats were well-matched across
After conditioning, the latencies to drink in the boxes were longer and the rats drank less, reflecting fear conditioning to context measured on the reshaping day
Summary
Amongst the multiplicity of 5-hydroxytyptamine receptor subtypes, the 5-hydroxytyptamine (5-HT6) receptor in particular is located in brain regions involved in learning and memory (Fone, 2008; Ivachtchenko et al, 2016) Consistent with this receptor distribution, 5-HT6 receptor antagonists can improve learning and memory in a variety of procedures (Fone, 2008; Ivachtchenko et al, 2016). A similar fear conditioning procedure (suppression of drinking after conditioning with footshock) was used to test the prediction that treatment with the 5-HT6 agonist EMD386088 would reduce LI, by restoring conditioning to the pre-exposed stimuli. EMD386088 was administered at 5 mg/kg, the dose previously identified to attenuate prior learning in a similar fear conditioning procedure (supplemental material). This dose restored fear conditioning that was attenuated because of cholinergic hypoactivity (Woods et al, 2012)
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