Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The specific radioligand binding of serotonin 5-HT1A and 5-HT2 receptors was determined in the frontal cortex and in the hypothalamus of Norway rats and silver foxes. Aggressive wild rats and silver foxes and animals selected for many generations for nonaggressive behavior towards man (domestication) were compared. The binding of the 5-HT1A receptors was found to be significantly higher in domesticated Norway rats and lower in domesticated foxes than in aggressive animals. The specific binding of the 5-HT2 receptors was found to be similar in aggressive and domesticated animals, both in rats and foxes. The data obtained indicate the involvement of 5-HT1A receptors in the hypothalamus into the process of domestication.
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PMID:[The effect of the domestication of Norway rats and silver foxes on the serotonin S1A- and S2-receptors of the brain]. 145 52

In silver foxes significant alterations in the activities of basic enzymes of neurotransmitter serotonin metabolism as well as in the densities of receptors caused by selection for the absence of the aggressive defensive reaction to man were demonstrated. In the midbrain and hypothalamus of animals selected for the absence of aggressive behavior, the activity of tryptophan hydroxylase, the key enzyme of serotonin biosynthesis, was found to be remarkably higher than in animals selected for highly aggressive behavior. Domesticated animals were characterized by low activity of the main enzyme of serotonin catabolism, monoamine oxidase type A, increased Michaelis constant km, and an unchanged maximum reaction rate (Vmax). No changes in the specific binding of [3H]-ketanserin and [3H]-8-OH-DPAT in the frontal cortex of domesticated foxes were revealed; however, in the hypothalamus, the low values of Bmax for the [3H]-8-OH-DPAT specific binding were observed, indicating the decreased density of the 5-HT1A receptors. It is assumed that the transformation of a wild aggressive animal into a domesticated one taking place during directional selection is caused by hereditary alterations favored by artificial selection in the activity of the main enzymes of serotonin metabolism and serotonin receptors.
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PMID:[Effect of domestication of the silver fox on the main enzymes of serotonin metabolism and serotonin receptors]. 924 68

This study was designed to assess the effects of imidazoline drugs on putative presynaptic imidazoline receptors modulating brain monoamine synthesis in vivo. The accumulation of 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxytryptophan (5-HTP) after decarboxylase inhibition was used as a measure of the rate of tyrosine and tryptophan hydroxylation in various brain regions of naive rats and after irreversible alpha2-adrenoceptor inactivation with EEDQ (1.6 mg/kg, i.p., 6 h). Clonidine (1-3 mg/kg), moxonidine (1-10 mg/kg) and rilmenidine (10 mg/kg) (mixed I1/alpha2 agonists) decreased dopa and 5-HTP synthesis in the cerebral cortex (14%-81%), hippocampus (27%-84%) and/or striatum (29%-56%), but these inhibitory effects were abolished in N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-treated rats. Similarly, the stimulatory effect of efaroxan (mixed I1/alpha2 antagonist; 10 mg/kg) on dopa synthesis in the cortex (77%) and hippocampus (57%) was abolished by EEDQ. The selective I1-ligand 2-endo-amino-3-exoisopropylbicyclo-heptane (AGN-192403; 5-10 mg/kg) did not modify dopa or 5-HTP synthesis in any brain region in naive or EEDQ-treated rats. Idazoxan (mixed I2/alpha2 antagonist; 20 mg/kg) increased dopa synthesis in the cortex (111%) and hippocampus (87%), but the stimulatory effects were abolished by EEDQ. Moreover, idazoxan and efaroxan decreased 5-HTP synthesis in the cortex (12%-34%) and hippocampus (30%-34%) in a manner sensitive to blockade by the 5-HT1A receptor antagonist WAY 100135. The selective I2-igands 2-(2-benzofuranyl)-2-imidazoline (2-BFI; 20 mg/kg) and 2-styryl-2-imidazoline (LSL 61122; 10 mg/kg) did not alter the synthesis of dopa or 5-HTP in the cortex or hippocampus. In striatum, 2-BFI (1-20 mg/kg) dose-dependently decreased dopa synthesis (ED50: 5.9 mg/kg), reduced dopamine levels (6%-36%) and increased those of its metabolites DOPAC (15%-95%) and HVA (24%-74%). The inhibitory effect of 2-BFI on dopa/dopamine synthesis in striatum remained unchanged after alkylation of imidazoline receptors with isothiocyanatobenzyl imidazoline (IBI; 60 mg/kg, 6 h) or blockade of these receptors with 2-(2-ethyl 2,3-dihydro-2-benzofuranyl)-2-imidazole (KU-14R; 7-20 mg/kg). Therefore, most imidazoline drugs modulated the synthesis of brain monoamines through interaction with alpha2-adrenoceptors or 5-HT1A receptors. The results do not provide functional evidence for the existence of presynaptic imidazoline receptors regulating the synthesis of monoamines in the rat brain.
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PMID:Effects of imidazoline receptor ligands on monoamine synthesis in the rat brain in vivo. 1046 34

The silver fox, a variant of the red fox (Vulpes vulpes), is a close relative of the dog (Canis familiaris). Cytogenetic differences and similarities between these species are well understood, but their genomic organizations have not been compared at higher resolution. Differences in their behavior also remain unexplained. Two silver fox strains demonstrating markedly different behavior have been generated at the Institute of Cytology and Genetics of the Russian Academy of Sciences. Foxes selected for tameness are friendly, like domestic dogs, while foxes selected for aggression resist human contact. To refine our understanding of the comparative genomic organization of dogs and foxes, and enable a study of the genetic basis of behavior in these fox strains, we need a meiotic linkage map of the fox. Towards this goal we generated a primary set of fox microsatellite markers. Four hundred canine microsatellites, evenly distributed throughout the canine genome, have been identified that amplify robustly from fox DNA. Polymorphism information content (PIC) values were calculated for a representative subset of these markers and population inbreeding coefficients were determined for tame and aggressive foxes. To begin to identify fox-specific single nucleotide polymorphisms (SNPs) in genes involved in the neurobiology of behavior, fox and dog orthologs of serotonin 5-HT1A and 5-HT1B receptor genes have been cloned. Sequence comparison of these genes from tame and aggressive foxes reveal several SNPs. The close relationship of the fox and dog enables canine genomic tools to be utilized in developing a fox meiotic map and mapping behavioral traits in the fox.
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PMID:A marker set for construction of a genetic map of the silver fox (Vulpes vulpes). 1522 Mar 84

The review summarizes the results of long-term studies on the role of the brain mediator serotonin and genetic predisposition to various types of defensive behavior. The involvement of the serotonergic brain system in the mechanisms of genetic control of both active and passive defensive responses has been established using silver foxes, Norway rats of S40 selection for low and high aggressiveness to humans, aggressive mice with genetic knockout of monoaminoxidase A, and S40 rats selected for predisposition to passive defensive response of freezing (catalepsy). The changes in the serotonergic 5-HT1A-brain receptors of rats genetically predisposed to different strategies of defensive behavior were similar. However, the activity of the key enzyme of serotonin biosynthesis and the brain structures, in which serotonin metabolism was altered, significantly differed with regard to the preferred strategy. The conclusion was drawn that the 5-HT1A-receptors and enzymes of serotonin metabolism in the brain are involved in implementing genetic control of defensive behavior. Expression of the 5-HT1A-brain receptors was suggested to determine the levels of fear and anxiety and, consequently, the predisposition to defensive behavior, whereas the preferred strategy of defensive response (active or passive defensive) depends on genetically determined features of serotonin metabolism in the brain structures.
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PMID:[The role of brain serotonin in the expression of genetically determined defensive behavior]. 1534 Dec 67

Aggressive behaviour exhibited by domestic pigs following encounters with unfamiliar individuals is a serious welfare and economical problem. Aggression resulting in skin lesions is similarly prevalent in prepubertal pigs of either sex. Little is known about the neural circuits and neuropeptides that control aggression in the pig. Because there is evidence for the involvement of the vasopressin and serotonergic systems in the regulation of aggressive behaviour in male mammals, we sought differences using quantitative in situ hybridisation of vasopressin and serotonin 1A receptor (5-HT1A) mRNA expression within specific brain regions of aggressive and nonaggressive prepubertal female pigs. The number of cells expressing vasopressin mRNA was significantly higher in aggressive pigs in the medial amygdala, lateral septum (LS) and showed a similar trend in the bed nucleus of the stria terminalis (BnST) but not the paraventricular nucleus (PVN) or supraoptic nucleus. The 5-HT1A receptor was widely expressed through the porcine brain and a significantly lower intensity (silver grain density) of 5-HT1A mRNA expression was observed in the BnST. In the medial amygdala and LS fewer cells expressed 5-HT1A mRNA in aggressive pigs but no differences were found in the PVN. In the absence of inbred strains or selection lines, these findings have shown that prior identification of phenotypic behavioural extremes in a population in advance of neural studies is a useful technique. Moreover, these findings support a central role for vasopressin and serotonin in the mediation of high trait aggression in prepubertal female pigs.
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PMID:Resident-intruder trait aggression is associated with differences in lysine vasopressin and serotonin receptor 1A (5-HT1A) mRNA expression in the brain of pre-pubertal female domestic pigs (Sus scrofa). 1615 81

The inferior parietal lobule (IPL) of the macaque monkey integrates sensory information as a prerequisite for reaching and grasping movements. Electrophysiological data suggest that the convexity of the IPL is heterogeneous along its rostro-caudal axis. Cytoarchitecture reflects this functional diversity. However, various parcellations have been proposed so far, ranging from one homogeneous region to four areas. In order to obtain a more valid anatomical map of the IPL, we studied the distribution pattern of serotonin 5-HT1A binding sites (i.e., the domain of synaptic transmission and cortical information processing) and cytoarchitecture with an observer-independent technique (thus avoiding the subjectivity inherent in visually guided microstructural parcellations). We cut with a cryostat microtome four unfixed macaque hemispheres and processed sections for 5-HT1A binding sites with [3H]8-OH-DPAT receptor autoradiography or for cell bodies with a modified silver stain. We digitized the autoradiographs and the histological sections and extracted from the cortex of the IPL equidistant density profiles oriented vertically to the cortical layers. We then compared groups of neighboring profiles with multivariate statistics expecting to see a significant difference in profile shape at the interface between two cortical areas. These positions were compared between 5-HT1A autoradiographs (neurochemical borders) and adjacent histological sections (cytoarchitectonic borders). Neurochemical and cytoarchitectonic borders showed a good topographical correspondence and revealed three areas arranged in a rostro-caudal sequence along the convexity of the IPL. Dorsally, the areas extend approximately 1 mm into the depth of the lateral bank of the intraparietal sulcus. Their ventral border lies on the convexity of the IPL close to the shoulder of the lateral sulcus. The three areas are in close agreement with areas PF, PFG, and PG as defined by Pandya and Seltzer (J Comp Neurol 204:196-210, 1982) and Gregoriou et al. (Program No. 919.5, Abstract Viewer/Itinerary Planner, Washington, Society for Neuroscience, 2003). The neurochemical and cytoarchitectonic data show that a complex structural framework underlies the functional heterogeneity along the rostro-caudal axis of the IPL, e.g., the representation of different types of arm and hand actions in different sectors of the monkey's workspace.
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PMID:The macaque inferior parietal lobule: cytoarchitecture and distribution pattern of serotonin 5-HT1A binding sites. 1618 22