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The effects of ritanserin, RU 24969 and 8-OH-DPAT on latent inhibition in the rat

Department of Psychology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK

Helen Hodges

Department of Psychology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK

Jeffrey A. Gray

Department of Psychology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK

When animals are exposed to a stimulus that has no consequences they are subsequently impaired in learning that this stimulus predicts an important event, such as footshock. This retarding effect of stimulus pre-exposure is called latent inhibition (LI) and is reliably disrupted by amphetamine, antipsychotics having an opposite effect. The present experiments investigated whether agents which affect serotonergic transmission also attenuate LI, using a conditioned suppression of drinking procedure. The results showed that the 5-HT₂ antagonist ritanserin (2.0 mg/kg), and the 5-HT_1b agonist RU 24969 (0.5 and 10.0 mg/kg) attenuated LI by increasing learning in pre-exposed animals, whilst the effects of the 5-HT_1a agonist 8-OH-DPAT (0.38 mg/kg), though in a similar direction, were not significant. These experiments provide partial support for the involvement of serotonin in LI. Since amphetamine-induced attenuation of LI has been proposed as a model for the attentional deficits found in acute schizophrenia, these results are discussed in terms of the possible involvement of reduced serotonergic function in schizophrenic attentional disorder.

Key Words: 5-hydroxytryptamine • ritanserin • RU 24969 • 8-hydroxy-2-(di-n-propylamino)tetralin • latent inhibition; rat

Journal of Psychopharmacology, Vol. 7, No. 1 suppl, 63-71 (1993)
DOI: 10.1177/026988119300700110


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