Increased cortical serotonin 5-HT2A receptor density in subjects

JAVIER GONZÁLEZ-MAESO; NOELIA V. WEISSTAUB; MINGMING ZHOU; LUIS F.CALLADO; JAY A. GINGRICH; J. JAVIER MEANA; STUART C. SEALFON

San Diego

Congreso; Society for Neuroscience 37th Annual Meeting; 2007

The psychoactive effects of hallucinogenic drugs (HDs) such as lysergic aciddiethylamide (LSD) or psilocybin share several features with schizophrenia (SZ)including perceptual disturbances, sensory processing, cognition, changes inbrain metabolism, and self-representation. We have recently shown that micewith disrupted serotonin 5-HT2A receptor (2AR) signalling capacity (htr2A-/- mice)are insensitive to the behavioural effects of HDs. We studied as a model of acutepsychosis the neuronal and behavioural responses induced by HDs in animalschronically treated with antipsychotics. Interestingly, the cellular and behaviouralresponses induced by LSD after chronic antipsychotic were undistinguishablefrom the responses induced by the closely related but non-HD lisuride. This ledus to reason that 2AR expression may be altered in SZ. The onset of psychosisusually occurs in later adolescence or early adulthood, and several studies haveshown that hallucinations and delusions become less severe as time progresses.We studied the relationship of 2AR densities with aging, and [3H]ketanserinbinding displayed a highly significant negative correlation with age. Inconcordance with this clinical feature, the ages of SZ subjects without treatmentincluded in the present study were 34 ± 2 years. We thus determined the[3H]ketanserin binding properties in postmortem human brain cortex of SZsubjects and controls who were matched by gender, age, and postmortem delay.The 2AR density was significantly higher in untreated SZ subjects. In addition,there were no differences in the density of 2AR in antipsychotic-treated SZcompared to controls. Overall, these data suggest that the higher density of 2ARmay contribute to positive symptoms in patients with SZ.