Hippocampal 5-hydroxytryptamine receptors: abnormalities in postmortem brain from schizophrenic subjects
Section snippets
Materials and methods
2-(N,N-Di[2,3(n)-3H]proplyamino-8-hydroxy-1,2,3,4-tetrahydronapthalene ([3H]8-OH-DPAT), [3H]sumatriptan, [3H]GR113808 and [3H]microscales™ were obtained from Amersham Biosciences whilst [3H]ketanserin hydrochloride was obtained from New England Nuclear. BAS-TR© plates came from Fuji Photo Film, Tokyo, Japan. Serotonin hydrochloride, methiothepin hemioxalate and spiperone hydrochloride were purchased from Sigma Aldrich, as were all other laboratory reagents.
Results
All data sets were shown not to differ from a Gaussian distribution.
Discussion
Under the conditions used in this study [3H]8-OH-DPAT would bind predominantly to the 5-HT1AR (Dean et al., 1999), [3H]ketanserin to the 5-HT2AR (Dean and Hayes, 1996), [3H]GR 11808 to the 5-HT4R (Dean et al., 1999) and [3H]sumatriptan to both the 5-HT1DR and 5-HT1FR (Pascual et al., 1996). Hence, as in two previous studies Burnet et al., 1996, Hashimoto et al., 1991, our data failed to show a change in the density of 5-HT1A R in the hippocampus from subjects with schizophrenia. These findings
Acknowledgements
This research was funded by NH&MRC Project Grant #114253, The Victorian State Government and The Rebecca L. Cooper Medical Research Foundation. The authors thank Jaclyn McKenzie and Robyn Bradbury for their technical assistance as well as Chris Hill, Nicholas Keks and Ken Opeskin for their contributions to tissue collection and postmortem diagnosis.
References (37)
- et al.
Serotonin and hallucinogens
Neuropsychopharmacology
(1999) Evidence for altered trisynaptic circuitry in schizophrenic hippocampus
Biol. Psychiatry
(1999)- et al.
5-HT1A and 5-HT2A receptor mRNAs and binding site densities are differentially altered in schizophrenia
Neuropsychopharmacology
(1996) A theory of the evolutionary origins of psychosis
Eur. Neuropsychopharmacol
(1995)- et al.
Decreased frontal cortical serotonin2A receptors in schizophrenia
Schizophr. Res
(1996) - et al.
No change in the density of the serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex from subjects with schizophrenia
Neurochem. Int
(1999) - et al.
Studies on serotonergic markers in the human hippocampus: changes in subjects with bipolar disorder
J. Affect. Disord
(2003) - et al.
Selective serotonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a randomised controlled trial
Lancet
(2001) - et al.
Decreased hippocampal expression of a glutamate receptor gene in schizophrenia
Lancet
(1991) - et al.
Increase in serotonin 5-HT1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia
Life Sci
(1991)
Serotonin receptors in the human brain: I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites
Brain Res
Tissue pH as an indicator of mRNA preservation in human post-mortem brain
Brain Res., Mol. Brain Res
The flinders sensitive line rats, a genetic model of depression, show abnormal serotonin receptor mRNA expression in the brain that is reversed by 17beta-estradiol
Brain Res., Mol. Brain Res
Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison
Lancet
[3H]sumatriptan binding sites in human brain: regional-dependent labelling of 5-HT1D and 5-HT1F receptors
Eur. J. Pharmacol
5-HT 1B/D receptor antagonists
Gen. Pharmacol
Ligands for the investigation of 5-HT autoreceptor function
Brain Res. Bull
Positive and negative symptoms in schizophrenia
Psychiatry Res
Cited by (21)
Increased amygdala and decreased hippocampus volume after schedule-induced polydipsia in high drinker compulsive rats
2020, Behavioural Brain ResearchCitation Excerpt :Reduced 5-HT2A binding is reported in cortical areas in high compulsive rats [23], companion dogs with a compulsive behavior [24] and drug-naïve OCD patients [25]. Post-mortem studies in schizophrenia patients, show a 5-HT2A reduction within prefrontal cortex [26,105–109) and hippocampus [110] when compared to healthy controls (for review, see: [27]). This extensive evidence adds to the hypothesis of its implication in cortical and amygdaloid regulation of emotion-based behaviors [5].
Serotonin and schizophrenia
2020, Handbook of Behavioral NeuroscienceAlterations in the serotonin system in schizophrenia: A systematic review and meta-analysis of postmortem and molecular imaging studies
2014, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Both ligands however lack specificity for 5-HT2A receptors, and show appreciable binding to 5-HT1A, Dopamine D2 and other receptors as well (Peroutka and Snyder, 1979), which may have confound the results. The results from postmortem studies using [3H]ketanserin, a more selective 5-HT2A/C receptor ligand, were more consistent with nine out of fourteen studies finding decreased binding in patients with schizophrenia compared to controls in prefrontal cortex (Mita et al., 1986; Burnet et al., 1996; Dean and Hayes, 1996; Kouzmenko et al., 1999; Matsumoto et al., 2005; Dean et al., 2008), superior temporal gyrus (Pralong et al., 2000; Kang et al., 2009) and hippocampus (Scarr et al., 2004) (Supplementary Table 3). In contrast, two recent large studies found increased binding in prefrontal cortex, but only in antipsychotic free patients (González-Maeso et al., 2008; Muguruza et al., 2012); suggesting antipsychotic treatment may alter 5-HT2A receptor binding.
Effects of olanzapine and betahistine co-treatment on serotonin transporter, 5-HT<inf>2A</inf> and dopamine D<inf>2</inf> receptor binding density
2013, Progress in Neuro-Psychopharmacology and Biological PsychiatrySex differences and the role of estrogen in animal models of schizophrenia: Interaction with BDNF
2013, NeuroscienceCitation Excerpt :Despite these findings, the exact neurochemical mechanisms involved in the postulated interaction between estrogens and BDNF, remain to be elucidated. Serotonin receptors have been implicated in the development of schizophrenia and the action of antipsychotic drugs (Meltzer, 1999; Scarr et al., 2004). Several clinical and preclinical studies have shown an interaction of serotonin, BDNF and sex steroid hormones although the results have been variable and these studies have not necessarily focused on schizophrenia (Cyr et al., 2002).