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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various in vitro models have been developed to study ischemia and/or hypoxia. In the present experiment, we examined whether hypoxia/hypoglycemia (ischemia) in rat hippocampal slices reduced the 2-deoxyglucose (2-DG) uptake and CA1 field potentials evoked by stimulation of Schaffer collaterals. Autoradiograms revealed that ischemia for 15 or 20 min reduced 2-DG uptake in the stratum radiatum of the CA1 and the dentate gyrus. Similarly, the CA1 field potentials of slices exposed to ischemia for 15 and 20 min decreased by about 70 and 90% after a 6-h washout. In the second experiment, we evaluated the neuroprotective effect of the 5-HT1A receptor agonists 8-OH-DPAT and buspirone, and the 5-HT2 receptor antagonists cyproheptadine, mianserin and ketanserin on deficits of 2-DG uptake and Schaffer-CA1 field potentials induced by ischemia. The 5-HT1A receptor agonists and 5-HT2 receptor antagonists exhibited significant neuroprotective actions against ischemia-induced deficits. Therefore, impairments of 2-DG uptake and CA1 field potentials induced by ischemia may be good markers of ischemia-induced functional deficits. The attenuating action of 5-HT1A receptor agonists and 5-HT2 receptor antagonists were assessed using this model of ischemia.
Eur J Pharmacol 1992 Dec 08
PMID:Ischemia-induced impairment of 2-deoxyglucose uptake and CA1 field potentials in rat hippocampal slices: protection by 5-HT1A receptor agonists and 5-HT2 receptor antagonists. 147 60

The stimulus effects of ibogaine were compared with those of yohimbine, an alpha 2-adrenoceptor antagonist, 2,5-dimethoxy-4-methylamphetamine (DOM), a 5-hydroxytryptamine2 (5-HT2) agonist, and lysergic acid diethylamide (LSD), a nonspecific 5-HT agonist. Rats were trained with either yohimbine (6 mg/kg), DOM (0.6 mg/kg), or LSD (0.1 mg/kg) vs. no treatment in a two-lever discrimination task. Tests of generalization were then conducted with ibogaine. In yohimbine-trained animals, 39.7% of responses following ibogaine (15 mg/kg) were on the drug-appropriate lever, but this response level was not significantly different from no treatment-appropriate responding. A response distribution that was significantly different from responding under both drug and no treatment training conditions was observed in DOM-trained rats after administration of 15 mg/kg ibogaine. Pizotyline (BC-105) blocked all DOM-appropriate responding produced by ibogaine. In LSD-trained animals, 20 mg/kg ibogaine mimicked LSD. Pizotyline blocked LSD-appropriate responding produced by ibogaine in five of six animals. The present data suggest the involvement of 5-HT2 receptor activity, and the possibility of a 5-HT1A contribution, in the stimulus properties of ibogaine.
Pharmacol Biochem Behav 1992 Dec
PMID:Stimulus effects of ibogaine in rats trained with yohimbine, DOM, or LSD. 147 6

Although numerous subtypes of serotonin [5-hydroxytryptamine (5-HT)] receptors have been identified in the newborn rat by radioligand binding studies, there have been few studies of the functional significance of these early receptors, most without the benefit of selective drugs. We performed acute dose-response and time course behavioral studies in 1-day-old rats with the putative selective agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-HT1A), 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H-indole (RU 24969) (5-HT1B), and (+-)1-(2,5-dimethoxy-4-iodo-phenyl aminopropane)-2 (DOI) (5-HT2/1C). The agonists induced distinctive behavioral syndromes. The DOI syndrome mainly included rudiments of forepaw myoclonus and dystonic limb postures, but no shaking behavior (head shakes or wet-dog shakes) or spinal myoclonus, two key reference behaviors for its effects in adult rats. The most distinctive feature of the 8-OH-DPAT-induced syndrome was flat body posture. RU 24969 most significantly increased locomotor activity, inducing propulsive movements with episodic rests and sudden hindlimb jerks. These studies suggest that functional and differential activity of 5-HT1A, 5-HT1B, and 5-HT2/1C receptors occurs much earlier in the rat than previously appreciated. The absence of DOI-induced shaking behavior and spinal myoclonus, however, suggests incomplete maturation at the level of the receptor or effector pathways for these behaviors.
Pharmacol Biochem Behav 1992 Dec
PMID:Serotonin receptor ontogeny: effects of agonists in 1-day-old rats. 147 12

Intracellular recording methods were used to study the actions of 5-hydroxytryptamine (5-HT) on 257 myenteric neurons in the guinea pig gastric antrum. Application of 5-HT caused three types of postsynaptic responses. A fast-activating depolarizing response was accompanied by a decreased input resistance and desensitized quickly to repeated applications. It was mediated by a 5-HT3 receptor. A slowly activating depolarization, accompanied by an increase in the input resistance and enhancement of the excitability, was mainly observed in after hyperpolarizing/type 2 neurons. It was suppressed by the prokinetic benzamide compound renzapride, while classical 5-HT1-4 receptor antagonists had no effect, suggesting the involvement of a 5-HT1p receptor as described in small intestinal neurons. A long-lasting hyperpolarizing response, accompanied by a decreased input resistance, was observed in a small subset of neurons. This response seemed to be mediated by a 5-HT1a receptor. Superfusion of 5-HT caused a dose-dependent inhibition of the stimulus-evoked nicotinic cholinergic fast excitatory postsynaptic potential (EPSP), which was mediated by a presynaptic 5-HT1a receptor. 5-HT also presynaptically inhibited the slow EPSP.
Am J Physiol 1992 Dec
PMID:Actions of 5-hydroxytryptamine on myenteric neurons in guinea pig gastric antrum. 147 91

Heterologous expression of the rat 5-HT1A receptor in stably transfected GH4C1 rat pituitary cells (clone GH4ZD10) and mouse Ltk- fibroblast cells (clone LZD-7) (Albert, P.R., Zhou, Q.-Y., VanTol, H.H.M., Bunzow, J.R., and Civelli, O. (1990) J. Biol. Chem. 265, 5825-5832) was used to characterize the cellular specificity of signal transduction by the 5-HT1A receptor. We demonstrate that the 5-HT1A receptor, acting via pertussis toxin-sensitive G proteins, can change its inhibitory signaling phenotype and become a stimulatory receptor, depending on the cell type, differentiation state, or intracellular milieu of the cell in which it is expressed. When expressed in pituitary GH4ZD10 cells, activation of 5-HT1A receptors decreased both basal and vasoactive intestinal peptide-enhanced cAMP accumulation and blocked (+/-)-Bay K8644-induced influx of calcium, inhibitory responses which are typical of neurons which endogenously express this receptor. Similarly, 5-hydroxytryptamine (5-HT) also inhibited adenylyl cyclase in fibroblast LZD-7 cells, reducing the forskolin-induced enhancement of cAMP levels by 50%, but did not alter basal cAMP levels. In contrast to GH4ZD10 cells, where 5-HT had no effect on basal or thyrotropin-releasing hormone-induced phosphatidylinositol turnover, 5-HT enhanced the accumulation of inositol phosphates and induced a biphasic increase in [Ca2+]i in LZD-7 cells. These dominant stimulatory actions of 5-HT, as well as the inhibitory effects, were absent in untransfected cells and displayed the potency and pharmacological specificity of the 5-HT1A receptor, indicating that the 5-HT1A subtype coupled to both inhibitory and stimulatory pathways in the fibroblast cell. The actions of 5-HT in GH and L cells were blocked by 24-h pretreatment with pertussis toxin, suggesting that inhibitory G proteins (Gi/G(o)) mediate both inhibitory and stimulatory signal transduction of the 5-HT1A receptor. However, the 5-HT-induced stimulatory pathway in fibroblasts was blocked selectively by acute (2-min) pretreatment with TPA, an activator of protein kinase C. This action of protein kinase C was potentiated by activation of protein kinase A, indicating that the expression of the stimulatory pathway of the 5-HT1A receptor in LZD-7 cells is modulated by second messengers.
J Biol Chem 1991 Dec 15
PMID:Cell-specific signaling of the 5-HT1A receptor. Modulation by protein kinases C and A. 166 Aug 81

The effects of two antidepressant drugs, amoxapine and amitriptyline, that belong to distinct chemical classes, have been examined on various biochemical parameters related to serotoninergic and opioidergic neurotransmission in the rat brain and spinal cord. In vitro binding studies showed that both amoxapine and amitriptyline interact in the nanomolar range with 5-HT2 receptors labelled by [3H]ketanserin in cortical membranes. By contrast, neither amoxapine nor amitriptyline can be considered as possible ligands of 5-HT1A and 5-HT1B receptors because their affinities for these sites are in the micromolar range (or even worse). Interestingly, amoxapine binds with a good affinity (IC50 = 0.30 microM) to 5-HT3 receptors labelled by [3H]zacopride in cortical membranes. Complementary experiments using the 5-HT3-dependent Bezold-Jarisch reflex confirmed that amoxapine really acts in vivo as a 5-HT3 antagonist (IC50 = 50 micrograms/kg i.v.), whereas amitriptyline is essentially inactive on 5-HT3 receptors. The second part of this study consisted of looking for possible changes in central 5-HT receptors 24 h after either a single or a repeated (for 14 days) treatment with amoxapine (10 mg/kg i.p. each day) or amitriptyline (10 mg/kg i.p.). A marked decrease in the density of 5-HT2 receptors was found in the cerebral cortex in both treatment groups. By contrast, neither 5-HT1A nor 5-HT1B receptors were significantly affected in any brain region studied. Finally we explored whether acute and/or chronic administration of amoxapine or amitriptyline affected the levels of opioid peptides and the mu and delta classes of opioid receptors in various regions of the brain and the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)
Encephale 1991 Dec
PMID:[Preclinical pharmacology of amoxapine and amitriptyline. Implications of serotoninergic and opiodergic systems in their central effect in rats]. 166 97

The regional distribution of [3H]idazoxan and [3H]rauwolscine was studied autoradiographically in human brain. [3H]Idazoxan binds with high affinity to alpha 2 adrenoceptors as well as to non-adrenergic sites (NAIBS). [3H]Rauwolscine, besides binding to alpha 2 adrenoceptors, also binds to 5-HT1A receptors. Both radioligands labelled the same population of alpha 2 adrenoceptors, defined as the epinephrine-displaceable binding component. The highest densities of alpha 2 adrenoceptors occur in the leptomeninges, cerebral cortex and claustrum; lower densities were visualised in the basal ganglia, thalamus, pons, substantia nigra, cerebellum and medulla oblongata; no alpha 2 adrenoceptors were detected in amygdala and nucleus ruber. NAIBS were present in all the examined brain areas, with the highest densities found in the basal ganglia and substantia nigra. The finding that certain brain regions, such as the amygdala, contained NAIBS but no detectable alpha 2 adrenoceptors, suggests that the binding sites are independent from each other. The regional distribution of 5-HT1A receptors labelled by [3H]rauwolscine is in agreement with previous studies using [3H]8-OH-DPAT.
Brain Res 1991 Dec 06
PMID:Autoradiographic distribution of alpha 2 adrenoceptors, NAIBS, and 5-HT1A receptors in human brain using [3H]idazoxan and [3H]rauwolscine. 166 6

Recent developments in the pharmacology of antidepressant drugs have focused on compounds that enhance the neurotransmission of serotonin (5-hydroxytryptamine; 5-HT), such as 5-HT uptake inhibitors. In addition, the 5-HT1A receptor partial agonist buspirone and other similarly structured compounds termed azapirones are also candidates for antidepressant therapy. The author reviews results from clinical and preclinical studies that support the efficacy of 5-HT1A receptor agonists as antidepressants. Initial clinical trials and animal behavior studies that predict clinical activity of antidepressant drugs have reported evidence favoring the antidepressant-like activity of 5-HT1A receptor partial agonists. Animal behavior studies have also examined the potential neurochemical mechanisms underlying the antidepressant effects of buspirone and related compounds. Evidence is reviewed that the antidepressant activity may be due to the activation of postsynaptic 5-HT1A receptors, although 5-HT1A receptor agonists also activate somatodendritic autoreceptors which diminish the release of 5-HT. Evidence does not support the involvement of a common metabolite 1-PP in the antidepressant activity of 5-HT1A receptor-selective azapirones. Few studies have examined the effects of chronic administration of 5-HT1A receptor agonists and their potential interaction with other receptors, such as 5-HT2 receptors.
J Clin Psychiatry 1991 Dec
PMID:Behavioral studies of serotonin receptor agonists as antidepressant drugs. 168 63

The effects of known anxiolytic agents and putative anxiolytic agents were assessed in mice in a fully automated 2-compartment light/dark test. Significant increases in lit area activities (e.g., time spent in the lit area, locomotor activity, rearing behavior) were used as possible indicators of anxiolytic-like action. The measurement found most consistent and useful for assessing antianxiety-like activity was the time mice spent in the lit area. The benzodiazepine, diazepam; the 5-HT1A agent, ipsapirone; and the 5-HT3 receptor antagonist, ondansetron, produced significant anxiolytic-like activity between doses of 1.0 to 10.0 mg/kg, 17.8 to 31.6 mg/kg, and 0.0001 to 1.0 mg/kg respectively. The 5-HT1A receptor agonist, 8-OH DPAT, also exhibited anxiolytic-like action between doses of 0.0005 to 3.16 mg/kg. In contrast, the peripheral 5-HT3 receptor agonist, N-phenylbiguanide; the antidepressant, imipramine; the neuroleptic, chlorpromazine; and the CNS stimulant, S(+)-amphetamine, did not display antianxiety-like activity. The positive results obtained for the three types of compounds (benzodiazepine, 5-HT1A, and 5-HT3) indicate that this fully automated light/dark apparatus may be useful for identifying known and putative anxiolytic agents.
Pharmacol Biochem Behav 1991 Dec
PMID:A fully automated light/dark apparatus useful for comparing anxiolytic agents. 168 62

Many antidepressants reverse arylpiperazine-induced hypothermia after acute treatment by a mechanism that does not seem to implicate monoamine uptake inhibition. Activity is found in reversing 1-(m-trifluoromethylphenyl)piperazine (TFMPP)-induced hypothermia by desipiramine 5 and 10 mg/kg and not by maprotiline 10 and 20 mg/kg. Clomipramine and fluoxetine with comparable serotonin uptake blocking potential do not have comparable TFMPP-reversing effects. A dibenzothiadiazepine compound (IM/P/3/4), hypothesized to have antidepressant activity though devoid of uptake blocking properties, was active at 10 and 20 mg/kg. Other classes of tricyclics such as neuroleptics (clozapine 5 and 10 mg/kg) and chlorpromazine (2 and 10 mg/kg) and the H1 antihistamines, promethazine (20 mg/kg) and cyproheptadine (10 mg/kg) are active, as well as the calcium antagonists nifedipine (10 mg/kg) and verapamil (10 mg/kg). We hypothesize that properties other than monoamine-uptake block which these compounds share (such as calcium-uptake inhibition) could be involved. Activity was also seen with the 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, at 0.05 and 0.25 mg/kg), and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT at 3 mg/kg) as well as with the muscarinic agonist oxotremorine (0.1 mg/kg).
Eur Neuropsychopharmacol 1991 Dec
PMID:m-trifluoromethylphenylpiperazine and m-chlorophenylpiperazine-induced hypothermia in mice is reversed by tricyclic antidepressants and other drugs. 168 12


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