Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug

Vandermaelen, Cam P.; Matheson, G.K.; Wilderman, R C; Patterson, Linda

doi:10.1016/0014-2999(86)90343-2

Cited by 222 publications

(60 citation statements)

References 29 publications

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“…Buspirone treatment, at doses similar to those used in the present study, reduces plasma 5-HT and its metabolite concentrations (Mizuki et al, 1994). An acute dose of buspirone in the rat significantly reduces 5-HT synthesis in the brain (Okazawa et al, 1999) and completely inhibits dorsal raphe nucleus firing (VanderMaelen et al, 1986), most likely by its action at presynaptic 5-HT 1A receptors. Together, this suggests that a reduction in 5-HT concentration in the human brain, as caused by tryptophan depletion or buspirone treatment, results in a disruption of PPI.…”

Section: Discussionmentioning

confidence: 95%

Estrogen Prevents 5-HT1A Receptor-Induced Disruptions of Prepulse Inhibition in Healthy Women

Gogos

Nathan

Guille

et al. 2005

Neuropsychopharmacol

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The sex steroid hormone, estrogen, has been proposed to be protective against schizophrenia. This study examined the effects of estrogen treatment on modulation of prepulse inhibition (PPI) by the serotonin-1A (5-HT 1A ) receptor partial agonist, buspirone. PPI is a model of sensorimotor gating, which is deficient in schizophrenia and other mental illnesses. A total of 11 healthy women were tested following four acute treatment conditions: placebo, buspirone (Buspar; 5 mg), estradiol (Estrofem; 2 mg), and combined buspirone and estradiol. Electromyogram activity was measured across three interstimulus intervals (ISI): 30, 60, and 120 ms. There was no significant effect of either drug treatment on startle amplitude or habituation. At 120 ms ISI, buspirone caused a significant disruption of PPI and pretreatment with estrogen prevented this disruption. Estrogen treatment, administered in the appropriate experimental conditions, prevented PPI deficits induced by 5-HT 1A receptor activation and may therefore also play a protective role in sensorimotor gating deficits in schizophrenia.

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Section: Discussionmentioning

confidence: 95%

Estrogen Prevents 5-HT1A Receptor-Induced Disruptions of Prepulse Inhibition in Healthy Women

Gogos

Nathan

Guille

et al. 2005

Neuropsychopharmacol

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“…Autoreceptor activation leads to reduced neuronal firing and thus reduced 5-HT activity in the brain (Invernizzi et al, 1991;Sharp et al, 1989;VanderMaelen et al, 1986) whereas post-synaptic 5HT 1A activation mediates behavioral effects of brain 5-HT (Carey et al, 2005;Rabiner et al, 2004). Half of the fish that were given 8-OH-DPAT at [0.25 mM] enhanced their amplitudes and the other half in this group reduced theirs after injection, raising the possibility that both types of Not all drugs we used cross the blood-brain barrier to the same extent.…”

Section: Discussionmentioning

confidence: 99%

Opposing actions of 5HT1A and 5HT2-like serotonin receptors on modulations of the electric signal waveform in the electric fish Brachyhypopomus pinnicaudatus

Allee

Markham

Salazar

et al. 2008

Hormones and Behavior

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Serotonin (5-HT) is an indirect modulator of the electric organ discharge (EOD) in the weakly electric gymnotiform fish, Brachyhypopomus pinnicaudatus. Injections of 5-HT enhance EOD waveform "masculinity", increasing both waveform amplitude and the duration of the second phase. This study investigated the pharmacological identity of 5-HT receptors that regulate the electric waveform and their effects on EOD amplitude and duration. We present evidence that two sets of serotonin receptors modulate the EOD in opposite directions. We found that the 5HT 1A R agonist 8-OH-DPAT diminishes EOD duration and amplitude while the 5HT 1A R antagonist WAY100635 increases these parameters. In contrast, the 5HT 2 R agonist α-Me-5-HT increases EOD amplitude but not duration, yet 5-HT-induced increases in EOD duration can be inhibited by blocking 5HT 2A/2C -like receptors with ketanserin. These results show that 5-HT exerts bi-directional control of EOD modulations in B. pinnicaudatus via action at receptors similar to mammalian 5HT 1A and 5HT 2 receptors. The discordant amplitude and duration response suggests separate mechanisms for modulating these waveform parameters. KeywordsSerotonin; Electric organ discharge; Communication signal; 5HT 1A receptor; 5HT 2 receptor; Social interaction; Dominance hierarchy Serotonin (5-HT) is a neuromodulator so ubiquitous that hardly any physiological function or behavior is free from its direct or indirect effects. As a result, a full account of neuroendocrine control of behavior requires a thorough assessment of 5-HT's function across a wide range of circumstances, even as the pervasive presence of 5-HT in the nervous system complicates unambiguous assessment of its functions. Particularly, serotonin is involved in the regulation of diametrically opposed behaviors, aggression and subordinance (Summers and Winberg, 2006). Serotonin activity rises in both dominant and subordinate males but rapidly returns to baseline in dominants while it stays chronically high in subordinates (Overli et al., 1999;Summers and Winberg, 2006). Prior social defeat or success during aggressive interactions affects future aggressive behaviors and the activity of the serotonergic system (Winberg et al., 1992;Winberg et al., 1997b). Furthermore, social experience affects the regulatory effect of serotonin on dominant behaviors via serotonin receptors 1A and 2A (Yeh et al., 1996). Pharmaceutical 5HT 1A agonists inhibit aggression or induce submissive behaviors in a wide range of non-mammalian vertebrates including green anoles (Deckel and Fuqua, 1998), Arctic charr (Hoglund et al., 2002;Winberg and Nilsson, 1993) Bell et al., 2007). In addition, 5HT 1A receptors operate as both postsynaptic receptors and as pre-synaptic autoreceptors to either suppress or stimulate stress responses in teleosts as they do in mammals (Hoglund et al., 2002). Despite the functionally and anatomically conserved nature of the serotonin system in vertebrates (Parent et al., 1984) and the abundance of data indicating a role for 5HT ...

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“…but comparable or lower than that of other 5-HT 1A receptor agonists, such as buspirone (11 mg/kg i.v. ; VanderMaelen et al, 1986), ipsapirone (30-125 mg/kg i.v. ; Basse-Tomusc and Rebec, 1986;Cox et al, 1993), or flesinoxan (21-108 mg/kg i.v.…”

Section: -Ht and Dual Action Antidepressant L Romero Et Almentioning

confidence: 99%

Modulation of Serotonergic Function in Rat Brain by VN2222, a Serotonin Reuptake Inhibitor and 5-HT1A Receptor Agonist

Romero

Celada

Martı́n-Ruiz

et al. 2002

Neuropsychopharmacol

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VN2222(1-(benzo [b]thiophen-3-yl)-3-[4-(2-methoxiphenyl piperazin-1-yl]propan-1-ol) is a potential antidepressant with high affinity for the serotonin transporter and 5-HT 1A receptors. Locally applied, VN2222 enhanced the extracellular 5-hydroxytryptamine (5-HT) concentration (5-HT ext ) in rat striatum to 780% of baseline whereas its systemic administration (1-10 mg/kg s.c.) reduced 5-HT ext . In the presence of citalopram, 8-OH-DPAT or VN2222 applied in medial prefrontal cortex reduced 5-HT ext . Fluoxetine, VN2222, and 8-OH-DPAT suppressed the firing rate of dorsal raphe 5-HT neurons (ED 50 : 790, 14.9, and 0.8 mg/kg i.v., respectively). These effects were antagonized by WAY 100635. Administration of VN2222 for 2 weeks desensitized 5-HT 1A receptors as assessed by microdialysis and single-unit recordings (ED 50 values for 8-OH-DPAT were 0.45 and 2.34 mg/kg i.v. for controls and rats treated with 6 mg/kg day VN2222). These results show that VN2222 is a mixed 5-HT reuptake inhibitor/5-HT 1A agonist that markedly desensitizes 5-HT 1A autoreceptors. These properties suggest that it may be a clinically effective dual action antidepressant drug.

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Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug

Cited by 222 publications

References 29 publications

Estrogen Prevents 5-HT1A Receptor-Induced Disruptions of Prepulse Inhibition in Healthy Women

Estrogen Prevents 5-HT1A Receptor-Induced Disruptions of Prepulse Inhibition in Healthy Women

Opposing actions of 5HT1A and 5HT2-like serotonin receptors on modulations of the electric signal waveform in the electric fish Brachyhypopomus pinnicaudatus

Modulation of Serotonergic Function in Rat Brain by VN2222, a Serotonin Reuptake Inhibitor and 5-HT1A Receptor Agonist

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