Swim stress inhibits 5-HT2A receptor-mediated head twitch behaviour in mice

Peričić, Danka

doi:10.1007/s00213-002-1357-y

Cited by 12 publications

(7 citation statements)

References 39 publications

(52 reference statements)

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“…Furthermore, the 5-HT 2A antagonist ketanserin failed to potentiate the anti-immobility effect for subactive doses of fluoxetine, citalopram, or fluvoxamine in the mouse forced swim test (Redrobe and Bourin, 1997). However, a recent report that swim stress induces a profound suppression of head shakes induced by 5-HT 2A receptor activation seriously questions whether negative effects of 5-HT 2A antagonists on the forced swim test might represent a false negative result due to a physiological confound with this paradigm (Pericic, 2003).The present antidepressant-like effects of M100907 both alone and in combination with the SSRI fluoxetine are probably mediated by blockade of central 5-HT 2A receptors. Although M100907 was not administered centrally, previously a highly selective 5-HT 2 receptor antagonist lacking CNS penetrance (xylamidine) failed to exert an antidepressant-like effect on DRL 72-s behavior (Marek et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

Marek

Martı́n-Ruiz

Abo

et al. 2005

Neuropsychopharmacol

112

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The addition of low doses of atypical antipsychotic drugs, which saturate 5-HT 2A receptors, enhances the therapeutic effect of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) in patients with major depression as well as treatment-refractory obsessive-compulsive disorder. The purpose of the present studies was to test the effects of combined treatment with a low dose of a highly selective 5-HT 2A receptor antagonist (M100907; formerly MDL 100,907) and low doses of a SSRI using a behavioral screen in rodents (the differential-reinforcement-of low rate 72-s schedule of reinforcement; DRL 72-s) which previously has been shown to be sensitive both to 5-HT 2 antagonists and SSRIs. M100907 has a B100-fold or greater selectivity at 5-HT 2A receptors vs other 5-HT receptor subtypes, and would not be expected to appreciably occupy non-5-HT 2A receptors at doses below 100 mg/kg. M100907 increased the reinforcement rate, decreased the response rate, and shifted the inter-response time distributions to the right in a pattern characteristic of antidepressant drugs. In addition, a positive synergistic interaction occurred when testing low doses of the 5-HT 2A receptor antagonist (6.25-12.5 mg/kg) with clinically relevant doses of the SSRI fluoxetine (2.5-5 mg/kg), which both exerted minimal antidepressant-like effects by themselves. In vivo microdialysis study revealed that a low dose of M100907 (12.5 mg/kg) did not elevate extracellular 5-HT levels in the prefrontal cortex over those observed with fluoxetine alone (5 mg/kg). These results will be discussed in the context that the combined blockade of 5-HT 2A receptors and serotonin transporters (SERT) may result in greater efficacy in treating neuropsychiatric syndromes than blocking either site alone.

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Section: Discussionmentioning

confidence: 99%

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

Marek

Martı́n-Ruiz

Abo

et al. 2005

Neuropsychopharmacol

112

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“…Importantly, however, ketanserin binding studies showed that this decrease in the HTR was not attributable to downregulation of 5-HT 2A receptors in frontal cortex, suggesting changes in other neural regions in response to this form of stress were modulating the HTR (Izumi et al 2002). Exposure of mice to ten minutes of swim stress resulted in a profound inhibition in the HTR induced by either DOI or 5-HTP (Pericic 2003). Additionally, genetic removal of the 5-HT 2A receptor neither ameliorated nor worsened the depression-like state induced by chronic unpredictable stress in either male or female mice, but did appear to protect against dyslipidemia induced by chronic unpredictable stress in wild-type male mice (Jaggar et al 2017).…”

Section: Stress Can Affect the Expression And Function Of 5-ht 2a Receptorsmentioning

confidence: 92%

Serotonin 2A receptors are a stress response system: implications for post-traumatic stress disorder

Murnane

2019

Behavioural Pharmacology

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Serotonin, one of the first neurotransmitters to be identified, is an evolutionarily old molecule that is highly conserved across the animal kingdom, and widely used throughout the brain. Despite this, ascribing a specific set of functions to brain serotonin and its receptors has been difficult and controversial. The 2A subtype of serotonin receptors (5-HT 2A receptor) is the major excitatory serotonin receptor in the brain and has been linked to the effects of drugs that produce profound sensory and cognitive changes. Numerous studies have shown that this receptor is upregulated by a broad variety of stressors, and have related 5-HT 2A receptor function to associative learning. This review proposes that stress, particularly stress related to danger and existential threats, increases the expression and function of 5-HT 2A receptors. It is argued that this is a neurobiological adaptation to promote learning and avoidance of danger in the future. Upregulation of 5-HT 2A receptors during stressful events forms associations that tune the brain to environmental cues that signal danger. It is speculated that life-threatening situations may activate this system and contribute to the symptoms associated with post-traumatic stress disorder. 3,4-Methylenedioxymethamphetamine, which activates 5-HT2A receptors, has been successful in the treatment of PTSD and has recently achieved status as a breakthrough therapy. An argument is presented that MDMA may paradoxically act though these same 5-HT2A receptors to ameliorate the symptoms of PTSD. The central thematic contention is that a central role of serotonin may be to function as a stress detection and response system.

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“…64-73% decrease in HTRs depending on the time of observation. [87] In apparent contrast to these findings, stress induced by 3 h of restraint enhanced sensitivity to the effects of 1.0 mg/kg (but not 2.0 mg/kg) DOI in rats. [88] Interestingly, obese Zucker rats that have an overactive hypothalamic-pituitary-adrenal system, resulting in a model of 'hypercorticism' with chronic, high levels of circulating corticosterone (which generally increases in rodents when exposed to stressful conditions) show a dramatically attenuated response to DOI compared to lean littermates.…”

Section: Environmental Factorsmentioning

confidence: 99%

“…Sprague-Dawley 1.25-3.0, NR 5-9 [114,32,131,66] Listar 1.0, (AE) 8 [113] OFA S-D 1.0-3.0, (AE) 5-7 [120] Mouse SAMP6 1.0, NR 83 [78] DBA-2J 1.0, (AE) 7 0 [65] C57Bl/6J (background) 1.0,1.5, (AE) 48,68 [119,121] C57Bl/6J 1.0, (+) 46 [76] C57Bl/6J 1.0, (AE) 30,40 [48,65] CAST/Ei 1.0, (+) 44 [76] SAMR1 1.0, NR 33 [78] 129S6/SvEv 2.0, NR 32 [94] Aston MF1 0.5, (AE) 3 2 [153] ICR 1.0, (AE) 28,29 [67,138] ICR 1.0, NR 25,26 [68,154] C3HeB/FeJ 1.0, (+) 28 [76] Aston MF1 1.0, NR 27 [141] 129Sv 2.0, NR 21 [194] C57Bl/6N 1.0, NR 19 [74] Balb/cJ 1.0, (+) 18 [76] NIH Swiss 1.0, (-) 18 [73] CBA 2.5, NR 16 [87] Swiss Webster 1.0, (-) 15 [73] Albino ICR 1.0, (AE) 20,25 [61,146] Albino ICR 1.25-2.5, (AE) 8,15 [4,56] Albino ICR 2.5, (-) 15 [56] Albino ICR 1.0, NR 8,9 [140,252] Albino ICR 2.5, (+) 8 [56] A/J 1.0, (+) 9 [76] NMRI 1.0, (AE) 8 [236] Dosing issues: problem of non-selectivity…”

Section: Species and Strainsmentioning

confidence: 99%

Head‐twitch response in rodents induced by the hallucinogen 2,5‐dimethoxy‐4‐iodoamphetamine: a comprehensive history, a re‐evaluation of mechanisms, and its utility as a model

Canal

Morgan

2012

Drug Testing and Analysis

170

200

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Two primary animal models persist for assessing hallucinogenic potential of novel compounds and for examining the pharmacological and neurobiological substrates underlying the actions of classical hallucinogens, the two-lever drug discrimination procedure and the drug-induced head-twitch response (HTR) in rodents. The substituted amphetamine hallucinogen, serotonin 2 (5-HT2) receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI) has emerged as the most popular pharmacological tool used in HTR studies of hallucinogens. Synthesizing classic, recent, and relatively overlooked findings, addressing ostensibly conflicting observations, and considering contemporary theories in receptor and behavioural pharmacology, this review provides an up-to-date and comprehensive synopsis of DOI and the HTR model, from neural mechanisms to utility for understanding psychiatric diseases. Also presented is support for the argument that, although both the two-lever drug discrimination and the HTR models in rodents are useful for uncovering receptors, interacting proteins, intracellular signalling pathways, and neurochemical processes affected by DOI and related classical hallucinogens, results from both models suggest they are not reporting hallucinogenic experiences in animals.

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Swim stress inhibits 5-HT2A receptor-mediated head twitch behaviour in mice

Cited by 12 publications

References 39 publications

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

Serotonin 2A receptors are a stress response system: implications for post-traumatic stress disorder

Head‐twitch response in rodents induced by the hallucinogen 2,5‐dimethoxy‐4‐iodoamphetamine: a comprehensive history, a re‐evaluation of mechanisms, and its utility as a model

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