Reduced 5-HT2A receptor binding in patients with mild cognitive impairment

Previous studies of patients with Alzheimer's disease (AD) have described reduced brain serotonin 2A (5-HT_2A) receptor density. It is unclear whether this abnormality sets in early in the course of the disease and whether it is related to early cognitive and neuropsychiatric symptoms.We assessed cerebral 5-HT_2A receptor binding in patients with mild cognitive impairment (MCI) and related 5-HT_2A receptor binding to clinical symptoms. Sixteen patients with MCI of the amnestic type (mean age 73, mean MMSE 26.1) and 17 age and sex matched control subjects were studied with MRI and [¹⁸F]altanserin PET in a bolus–infusion approach. A significant global reduction of 20–30% in 5-HT_2A binding (atrophy corrected) was found in most neocortical areas. Reduced 5-HT_2A binding in the striatum correlated significantly with Neuropsychiatric Inventory depression and anxiety scores. We conclude that widespread reductions in 5-HT_2A receptor binding were found in amnestic MCI, pointing at the presence of serotonergic dysfunction in prodromal AD. This may provide some of the pathophysiological background for the neuropsychiatric symptoms found in early AD.     

Effects of amyloid-β peptides on the serotoninergic 5-HT1A receptors in the rat hippocampus

A recent [¹⁸F]MPPF-positron emission tomography study has highlighted an overexpression of 5-HT_1A receptors in the hippocampus of patients with mild cognitive impairment compared to a decrease in those with Alzheimer's disease (AD) [Truchot, L., Costes, S.N., Zimmer, L., Laurent, B., Le Bars, D., Thomas-Antérion, C., Croisile, B., Mercier, B., Hermier, M., Vighetto, A., Krolak-Salmon, P., 2007. Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment. Neurology 69 (10), 1012-1017]. We used in vivo and in vitro neuroimaging to evaluate the longitudinal effects of injecting amyloid-β (Aβ) peptides (1-40) into the dorsal hippocampus of rats. In vivo microPET imaging showed no significant change in [¹⁸F]MPPF binding in the dorsal hippocampus over time, perhaps due to spatial resolution. However, in vitro autoradiography with [¹⁸F]MPPF (which is antagonist) displayed a transient increase in 5-HT_1A receptor density 7 days after Aβ injection, whereas [¹⁸F]F15599 (a radiolabelled 5-HT_1A agonist) binding was unchanged suggesting that the overexpressed 5-HT_1A receptors were in a non-functional state. Complementary histology revealed a loss of glutamatergic neurons and an intense astroglial reaction at the injection site. Although a neurogenesis process cannot be excluded, we propose that Aβ injection leads to a transient astroglial overexpression of 5-HT_1A receptors in compensation for the local neuronal loss. Exploration of the functional consequences of these serotoninergic modifications during the neurodegenerative process may have an impact on therapeutics targeting 5-HT_1A receptors in AD.     

Decreased prefrontal 5-HT2A receptor binding in subjects at enhanced risk for schizophrenia

The brain serotonin-2A receptor (5-HT_2AR) has been implicated in both the pathology of schizophrenia and the therapeutic action of atypical antipsychotics. However, little is known about the 5-HT_2AR status before the onset of schizophrenia and before the exposure to antipsychotics. We used [¹⁸F] altanserin and positron emission tomography (PET) in a pilot study of 6 individuals suspected to be at elevated risk for schizophrenia and seven age-matched controls to test the hypothesis that regional 5-HT_2AR binding is altered in the prodromal stages of schizophrenia. Distribution volume ratios (DVRs) as a proxy for 5-HT_2AR availability were significantly reduced in prefrontal cortex regions of at-risk subjects, implicating early abnormalities of serotonergic neurotransmission that antecede the onset of schizophrenia.     

In vivo evaluation of amyloid deposition and brain glucose metabolism of 5XFAD mice using positron emission tomography

Positron emission tomography (PET) has been used extensively to evaluate the neuropathology of Alzheimer's disease (AD) in vivo. Radiotracers directed toward the amyloid deposition such as [¹⁸F]-FDDNP (2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) and [¹¹C]-PIB (Pittsburg compound B) have shown exceptional value in animal models and AD patients. Previously, the glucose analogue [¹⁸F]-FDG (2-[(18)F]fluorodeoxyglucose) allowed researchers and clinicians to evaluate the brain glucose consumption and proved its utility for the early diagnosis and the monitoring of the progression of AD. Animal models of AD are based on the transgenic expression of different human mutant genes linked to familial AD. The novel transgenic 5XFAD mouse containing 5 mutated genes in its genome has been proposed as an AD model with rapid and massive cerebral amyloid deposition. PET studies performed with animal-dedicated scanners indicate that PET with amyloid-targeted radiotracers can detect the pathological amyloid deposition in transgenic mice and rats. However, in other studies no differences were found between transgenic mice and their wild type littermates. We sought to investigate in 5XFAD mice if the radiotracers [¹¹C]-PIB, and [¹⁸F]-Florbetapir could quantify the amyloid deposition in vivo and if [¹⁸F]-FDG could do so with regard to glucose consumption. We found that 5XFAD animals presented higher cerebral binding of [¹⁸F]-Florbetapir, [¹¹C]-PIB, and [¹⁸F]-FDG. These results support the use of amyloid PET radiotracers for the evaluation of AD animal models. Probably, the increased uptake observed with [¹⁸F]-FDG is a consequence of glial activation that occurs in 5XFAD mice.     

Autoradiographic mapping of serotonin 5-HT1A, 5-HT1D, 5-HT2A and 5-HT3 receptors in the aged human spinal cord

Quantitative autoradiography with selective radioligands was used to establish the respective distribution of serotonin 5-HT_1A, 5-HT_1D, 5-HT_2A and 5-HT₃ receptors at the cervical, thoracic and lumbar levels of the spinal cord from subjects who died at 81–94 years. A high density of 5-HT_1A receptors, labeled by [³H]8-hydroxy-2-(di-n-propylamino)tetralin ([³H]8-OH-DPAT), was found in the superficial layers of the dorsal horn, with a significant enrichment ( 20%) in the lumbar vs. the thoracic and cervical segments. In contrast, only very low specific labeling by [³H]8-OH-DPAT (i.e. less than 10% of that measured in the dorsal horn), was detected in the ventral horn. 5-HT_1D sites labeled by [¹²⁵I]serotonin-O-carboxymethyl-glycyl-iodo-tyrosinamide ([¹²⁵I]GTI) were also mainly located within the superficial layers of the dorsal horn, but no difference in their relative density was noted at the three levels of the spinal cord examined. 5-HT_2A sites labeled by [³H]ketanserin were found in the dorsal horn of the cervical segments but no specific binding of this radioligand could be detected at any other level of the spinal cord of such aged subjects. Finally, a high density of [³H]S-zacopride-labeled 5-HT₃ receptors was noted especially in the most superficial layer (lamina I) of the dorsal horn at all segments examined. These data provide anatomical support for a role of spinal serotonin especially in nociception processing.     

5-HT2A receptor levels increase in MPTP-lesioned macaques treated chronically with L-DOPA

Long-term L-3,4-dihydroxyphenylalanine (L-DOPA) treatment in Parkinson's disease (PD) is associated with motor complications such as dyskinesia. There are clear functional interactions between dopaminergic and serotonergic type 2A receptors (5-HT_2A)-mediated neurotransmission. Moreover, 5-HT_2A receptor antagonists can reduce L-DOPA-induced dyskinesia (LID). We hypothesized that enhanced 5-HT_2A-mediated neurotransmission may be involved in the genesis of L-DOPA-induced dyskinesia. Radioligand binding autoradiography, using [³H]-ketanserin, was performed to define 5-HT_2A receptor levels in brain tissue from macaques: 6 normal; 5 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned, parkinsonian macaques, without exposure to L-DOPA; 6 MPTP-lesioned, parkinsonian macaques, receiving a single administration of L-DOPA, and exhibiting no dyskinesia; and 6 MPTP-lesioned, parkinsonian, macaques chronically treated with L-DOPA, and exhibiting dyskinesia. 5-HT_2A receptor binding was increased in the caudate, putamen, and middle layers of the motor cortex in chronically L-DOPA-treated animals, by 50%, 50%, and 45% respectively, compared with normal macaques. 5-HT_2A binding was not significantly altered in parkinsonian, untreated, or parkinsonian, single treatment, nondyskinetic macaques, compared with normal. These data provide an anatomical basis for mechanisms to explain the efficacy of 5-HT_2A antagonists against dyskinesia.     

Effect of acute and chronic exercise on plasma amino acids and prolactin concentrations and on [3H]ketanserin binding to serotonin2A receptors on human platelets

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been shown to modulate various physiological and psychological functions such as fatigue. Altered regulation of the serotonergic system has been suggested to play a role in response to exercise stress. In the present study, the influence was investigated of acute endurance exercise and short-term increase in the amount of training on the concentrations of the 5-HT precursor tryptophan (TRP), of prolactin (PRL) and of branched-chain amino acids (BCAA) in the blood, as well as on the binding of [³H]ketanserin to the serotonin-2A (5-HT_2A) receptors on platelets. Nine healthy endurance-trained men were tested the day before (I) and after (II) a 9-day training programme. Samples of venous blood were drawn after an overnight fast and following 5?h of cycling. Fasted and post-exercise plasma concentrations of free TRP, BCAA and free TRP:BCAA ratio did not differ between I and II. A significant decrease of plasma BCAA (P?P?2A receptor [³H]ketanserin binding sites at I and II (P?3H]ketanserin for these binding sites were unaffected by an increase in the amount of training. The present results support the hypothesis that acute endurance exercise may increase 5-HT availability. This was reflected in the periphery by increased concentration of the 5-HT precursor free TRP, by increased plasma PRL concentration, and by a reduction of 5-HT_2A receptors on platelets. It remains to be resolved whether these alterations in the periphery occur in parallel with an increase in the availability of 5-HT in the brain.     

The Effects of Hypothyroidism on 5-HT1A and 5-HT2A Receptors and the Serotonin Transporter Protein in the Rat Brain

The effects of hypothyroidism on 5-HT_1A and 5-HT_2A receptors and the serotonin transporter protein were studied in thyroidectomized male Wistar rats in two experimental groups: 1) animals kept on an iodine-free diet (hypothyroid rats) and 2) animals kept on thyroxine (15 g/kg) for 21 days (giving normal thyroid hormone levels, euthyroid animals). Sham-operated rats served as controls. Binding of [³H]8-OH-DPAT with 5-HT_1A receptors and [³H]citalopram with the transporter protein in the hippocampus and midbrain showed no changes in hypothyroid rats as compared with controls. Conversely, there were significant decreases in [³H]ketanserin binding to 5-HT_2A receptors in the frontal cortex in hypothyroid rats as compared with controls; this decrease was reversed by thyroxine treatment. Thus, losses of cortical 5-HT_2A receptors appears to be the main consequence of hypothyroidism at the level of the serotonin system of the brain.     

Changes in 5-HT2A-mediated behavior and 5-HT2A- and 5-HT1A receptor binding and expression in conditional brain-derived neurotrophic factor knock-out mice

Changes in brain-derived neurotrophic factor (BDNF) expression have been implicated in the etiology of psychiatric disorders. To investigate pathological mechanisms elicited by perturbed BDNF signaling, we examined mutant mice with central depletion of BDNF (BDNF^2L/2LCk-cre). A severe impairment specific for the serotonin 2A receptor (5-HT_2AR) in prefrontal cortex was described previously in these mice. This is of much interest, as 5-HT_2ARs have been linked to neuropsychiatric disorders and anxiety-related behavior. Here we further characterized the serotonin receptor alterations triggered by BDNF depletion. 5-HT_2A ([³H]-MDL100907) and 5-HT_1A ([³H]-WAY100635) receptor autoradiography revealed site-specific alterations in BDNF mutant mice. They exhibited lower 5-HT_2A receptor binding in frontal cortex but increased binding in hippocampus. Additionally, 5-HT_1A receptor binding was decreased in hippocampus of BDNF mutants, but unchanged in frontal cortex. Molecular analysis indicated corresponding changes in 5-HT_2A and 5-HT_1A mRNA expression but normal 5-HT_2C content in these brain regions in BDNF^2L/2LCk-cre mice. We investigated whether the reduction in frontal 5-HT_2AR binding was reflected in reduced functional output in two 5-HT_2A-receptor mediated behavioral tests, the head-twitch response (HTR) and the ear-scratch response (ESR). BDNF^2L/2LCk-cre mutants treated with the 5-HT_2A receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) showed a clearly diminished ESR but no differences in HTR compared to wildtypes. These findings illustrate the context-dependent effects of deficient BDNF signaling on the 5-HT receptor system and 5-HT_2A-receptor functional output.     

Mapping of functional activity in the falcon visual system with [14C] 2-Deoxyglucose

Summary [¹⁴C] 2-Deoxyglucose uptake was mapped in the brain of one awake falcon which had one eye covered during the experiment, with the aim of providing tentative data on the identification of this bird's visual centers. Most of the structures with increased [¹⁴C] 2-Deoxyglucose uptake receive information from the exposed eye. Labeling was rather symmetrical in the hyperstriatum which receives bilateral projections from the visual thalamic centers.The results are largely consistent with what is known about the visual pathways in pigeons and owls. The falcon's visual Wulst as detected by the [¹⁴C] 2-Deoxyglucose labeling, is proportionally larger than that found in the pigeon. This result is consistent with the marked representation of the binocular visual field in the falcon's Wulst.Supported by grants 81/1138 of the Ministero delia Pubblica Istruzione and 82.00122.04 of the Consiglio Nazionale delle Ricerche     

Selective immunolesion of cholinergic neurons leads to long-term changes in 5-HT2A receptor levels in hippocampus and frontal cortex

Although loss of cholinergic neurons in the basal forebrain is considered a key initial feature in Alzheimer's disease (AD), changes in other transmitter systems, including serotonin and 5-HT_2A receptors, are also associated with early AD. The aim of this study was to investigate whether elimination of the cholinergic neurons in the basal forebrain directly affects 5-HT_2A receptor levels. For this purpose intraventricular injection of the selective immunotoxin 192 IgG-Saporin was given to rats in doses of either 2.5 or 5 μg. The rats were sacrificed after 1, 2, 4 and 20 weeks. 5-HT_2A protein levels were determined by western techniques in frontal cortex and hippocampus. A significant 70% downregulation in frontal cortex and a 100% upregulation in hippocampus of 5-HT_2A receptor levels were observed 20 weeks after the cholinergic lesion when using the highest dose of 192 IgG-Saporin. Our results show that cholinergic deafferentation leads to decreased frontal cortex and increased hippocampal 5-HT_2A receptor levels. This is probably a consequence of the interaction between the serotonergic and the cholinergic system that may vary depending on the brain region.     

Insulin receptors along the rat nephron: [125I] Insulin binding in microdissected glomeruli and tubules

Binding of [¹²⁵I] Tyr A¹⁴ human insulin ([¹²⁵I] insulin) was measured at 4°C in glomeruli and pieces of tubule microdissected from collagenase-treated rat kidneys. For glomeruli and all segments tested, total and non specific binding increased linearly with glomeruli number or tubular length. When determined with 4.0 nM labelled hormone, the distribution of specific binding sites (expressed as 10^–18 mol [¹²⁵I] insulin bound per glomerulus or mm tubule length) was as follows: glomerulus, 2.5±0.3; proximal convoluted tubule (PCT), 12.6±0.6; pars recta (PR), 4.0±2.3; thin descending limb (TDL), 0.6±0.2; thin ascending limb (TAL), 0.6±0.2; medullary thick ascending limb (MAL), 0.8±0.1; cortical ascending limb (CAL), 2.1±0.1; distal convoluted tubule (DCT), 5.6±1.1; cortical collecting tubule (CCT), 3.2±0.3 and outer medullary collecting tubule (MCT), 2.3±0.1. Specific [¹²⁵I] insulin binding to glomeruli and tubule segments was time- and dose-dependent, saturable, reversible after elimination of free labelled ligand, and inhibited by unlabelled human insulin. When analysed in Scatchard and Hill coordinates, the binding data revealed a negative cooperation in the interaction processes between [¹²⁵I] insulin and glomerular and tubular binding sites, with apparent dissociation constants and Hill coefficients of the following values: glomerulus, 0.6 nM and 0.60; PCT, 10.0 nM and 0.55; MAL, 4.3 nM and 0.80; CAL, 2.0 nM and 0.74; CCT, 7.6 nM and 0.80 and MCT, 1.0 nM and 0.57 respectively. The stereospecificity of nephron binding sites was assessed in competitive experiments showing that unlabelled bovine and procine insulins were as efficient as human insulin for displacing [¹²⁵I] insulin, whereas A and B chains of insulin and unrelated peptide hormones were almost inactive. These results indicate that the detected [¹²⁵I] insulin binding sites may correspond to physiological insulin receptors.Abbreviations used [¹²⁵I] Insulin [¹²⁵I] Tyr A¹⁴ human insulin - PCT proximal convoluted tubule - PR pars recta - TDL thin descending limb - TAL thin ascending limb - MAL medullary thick ascending limb - CAL cortical ascending limb - DCT distal convoluted tubule - CCT cortical collecting tubule - MCT outer medullary collecting tubule     

Hypothalamic serotonin-1A receptor binding measured by PET predicts the plasma level of dehydroepiandrosterone sulfate in healthy women

Serotonin modulates the activity of the hypothalamic–pituitary–adrenal (HPA) axis particularly via the serotonin-1A receptor (5-HT_1A). Therefore, the rationale of this positron emission tomography (PET) study was to investigate the influence of the 5-HT_1A receptor distribution in the human brain on plasma levels of dehydroepiandrosterone sulfate (DHEAS) and cortisol in vivo. Eighteen healthy female were measured with PET and the selective 5-HT_1A receptor radioligand [carbonyl-¹¹C]WAY-100635. Nine a priori defined brain regions (hypothalamus, orbitofrontal cortex, amygdala, hippocampus, anterior and posterior cingulate cortices, dorsal raphe nucleus, retrosplenial cortex, and insula) and the cerebellum (reference region) were delineated on coregistered MR images. DHEAS and cortisol plasma levels were collected by blood sampling in the morning of the PET day. Linear regression analysis of DHEAS plasma level as dependent variable and hypothalamic 5-HT_1A receptor binding potential (BP) as independent variable showed a highly significant association (r = .691, p = .002). The hypothalamic 5-HT_1A BP predicted 47.7% of the variability in DHEAS plasma levels. Regressions were borderline significant (p < .01, Bonferroni corrected threshold <.0056) between 5-HT_1A BP in the anterior cingulate and orbitofrontal cortices and free cortisol levels. No significant associations between DHEAS or cortisol and the 5-HT_1A receptor BP in other investigated brain regions were found. In conclusion, the serotonergic system may influence the DHEAS plasma level by modulating CRH and ACTH release via hypothalamic 5-HT_1A receptors as reported for cortisol before. As disturbances of the HPA axis as well as changes of the 5-HT_1A receptor distribution have been reported in affective disorders, future studies should focus on these interactions.     

Regional central serotonin receptor binding in rats treated chronically with high-dose 5-hydroxy-L-tryptophan

Summary The serotonin (5-HT) precursor 5-hydroxy-L-tryptophan (L-5-HTP) exerted differential regional effects on central 5-HT receptors in rats treated chronically by intraperitoneal injections of large incremental doses (50–200 mg/kg). There were significant reductions in B_max of agonist-labelled (-35%) and antagonist-labelled (-20%) 5-HT₂ sites in cortex but no changes in brainstem. K_d and n_H were unaffected by L-5-HTP. B_max of 5-HT₁ sites (unsubtyped) was reduced 16% in cortex and 18% in spinal cord, but the changes were not significant. Brainstem 5-HT₁ sites were unaffected. Studies at a single isotope concentration in other regions revealed significant reductions of antagonist-labelled 5-HT₂ specific binding in diencephalon (-26%) but not septum, and of 5-HT₁ binding in diencephalon (-25%) and cerebellum (-30%) but not in hippocampus or striatum. Absence of L-5-HTP-evoked changes in 5-HT receptors in brainstem may have implications for L-5-HTP-responsive and brainstem-mediated human myoclonic disorders.     

Age-related decline in nicotinic receptor availability with [(123)I]5-IA-85380 SPECT

Human postmortem studies have reported decreases with age in high affinity nicotine binding in brain. We investigated the effect of age on β₂-containing nicotinic acetylcholine receptor (β₂-nAChR) availability in eight brain regions of living human subjects using the ligand [¹²³I]5-IA-85380 ([¹²³I]5-IA) and single photon emission computed tomography (SPECT). Healthy, nonsmokers (N = 47) ranging in age from 18 to 85 were administered [¹²³I]5-IA using a bolus plus constant infusion paradigm and imaged 6–8 h later under equilibrium conditions. The effect of age on regional β₂-nAChR availability (V_T, regional brain activity/free plasma parent, a measure proportional to the binding potential) was analyzed using linear regression and Pearson's correlation (r). Age and regional β₂-nAChR availability were inversely correlated in seven of the eight brain regions analyzed, with decline ranging from 32% (thalamus) to 18% (occipital cortex) over the adult lifespan, or up to 5% per decade. These results in living human subjects corroborate postmortem reports of decline in high affinity nicotine binding with age and may aid in elucidating the role of β₂-nAChRs in cognitive aging.     

LP-211 is a brain penetrant selective agonist for the serotonin 5-HT7 receptor

We have determined the pharmacological profile of the new serotonin 5-HT₇ receptor agonist N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211). Radioligand binding assays were performed on a panel of 5-HT receptor subtypes. The compound was also evaluated in vivo by examining its effect on body temperature regulation in mice lacking the 5-HT₇ receptor (5-HT₇^−/−) and their 5-HT₇^+/+ sibling controls. Disposition studies were performed in mice of both genotypes. It was found that LP-211 was brain penetrant and underwent metabolic degradation to 1-(2-diphenyl)piperazine (RA-7). In vitro binding assays revealed that RA-7 possessed higher 5-HT₇ receptor affinity than LP-211 and a better selectivity profile over a panel of 5-HT receptor subtypes. In vivo it was demonstrated that LP-211, and to a lesser degree RA-7, induced hypothermia in 5-HT₇^+/+ but not in 5-HT₇^−/− mice. Our results suggest that LP-211 can be used as a 5-HT₇ receptor agonist in vivo.     

5-HT2A receptor inactivation potentiates the acute antidepressant-like activity of escitalopram: involvement of the noradrenergic system

Evidence suggests that the serotonin 2A receptor (5-HT_2AR) modulates the therapeutic activity of selective serotonin reuptake inhibitors (SSRIs). Indeed, among the genetic factors known to influence the individual response to antidepressants, the HTR2A gene has been associated with SSRIs response in depressed patients. However, in these pharmacogenetic studies, the consequences of HTR2A gene polymorphisms on 5-HT_2AR expression or function are lacking and the precise role of this receptor is still matter of debate. This study examined the effect of 5-HT_2AR agonism or antagonism with DOI and MDL100907, respectively, on the serotonergic system and the antidepressant-like activity of the SSRI escitalopram in mouse. The 5-HT_2AR agonist DOI decreased the firing rate of 5-HT neurons in the dorsal raphe (DR) nucleus of 5-HT_2AR^+/+ anesthetized mice. This inhibitory response persisted in 5-HT_2CR^?/? but was completely blunted in 5-HT_2AR^?/? mutants. Moreover, the suppressant effect of DOI on DR 5-HT neuronal activity in 5-HT_2AR^+/+ mice was attenuated by the loss of noradrenergic neurons induced by the neurotoxin DSP4. Conversely, in 5-HT_2AR^+/+ mice, the pharmacological inactivation of the 5-HT_2AR by the selective antagonist MDL100907 reversed escitalopram-induced decrease in DR 5-HT neuronal activity. Remarkably, in microdialysis experiments, a single injection of escitalopram increased cortical extracellular 5-HT, but not NE, levels in awake 5-HT_2AR^+/+ mice. Although the addition of MDL100907 did not potentiate 5-HT neurotransmission, it allowed escitalopram to increase cortical NE outflow and consequently to elicit an antidepressant-like effect in the forced swimming test. These results suggest that the blockade of the 5-HT_2AR may strengthen the antidepressant-like effect of escitalopram by facilitating the enhancement of the brain NE transmission. They provide support for the use of atypical antipsychotics with SSRIs as a relevant antidepressant augmentation strategy.     

Contribution of 5-HT1A serotonin receptors of the brain to the regulation of hereditary catalepsy

Selective agonists 5-HT_1A of serotonin receptors (8-OH-DPAT and flezinoxan) had an inhibitory effect on the manifestation of hereditary catalepsy in mice and rats. No differences were revealed in specific binding of³H-8-OH-DPAT to 5-HT_1A receptors in the striatum of either cataleptic or noncataleptic mice and rats. Nonetheless, an increase of the density of these receptors was observed in the frontal cortex of CBA mice predisposed to catalepsy in comparison with mice of the noncataleptic C57Bl strain. The data indicate a contribution of 5-HT_1A receptors to the regulation of hereditary catalepsy. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 633–635, December, 1994 Presented by V. P. Kaznacheev, Member of the Russian Academy of Medical Sciences