Direct and indirect 5-HT receptor agonists produce gender-specific effects on locomotor and vertical activities in C57 BL/6J mice

Brookshire, Bethany R.; Jones, Sara R.

doi:10.1016/j.pbb.2009.08.008

Cited by 36 publications

(24 citation statements)

References 48 publications

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“…Similar to our findings, other groups have reported that DOI increases locomotor activity in mice (Darmani et al, 1996; Brookshire and Jones, 2009). There is also evidence that low doses of DOM can increase locomotor activity and reduce rearing behavior in ddN mice (Yamamoto and Ueki, 1975).…”

Section: Discussionsupporting

confidence: 93%

“…Therefore, these discrepant findings are most likely a consequence of differences in study design, and the duration of the open field studies with DOI and TCB-2 may not have been long enough to detect hyperactivity induced by those agents. In contrast to our BPM studies, which were conducted during the dark phase of the light-dark cycle, Fox et al (2010) tested DOI and TCB-2 during the light phase; it is unlikely, however, that this contributed to the discrepant findings because DOI has also been shown to induce hyperactivity during the light-phase (Brookshire and Jones, 2009). …”

Section: Discussionmentioning

confidence: 60%

“…Importantly, DOI does not increase locomotor activity in 5-HT 2A knockout mice, indicating that the effect is a consequence of 5-HT 2A receptor activation (Halberstadt et al, 2009). Although other groups have also found that DOI and DOM increase locomotor activity in mice (Yamamoto and Ueki et al, 1975; Darmani et al, 1996; Brookshire and Jones, 2009), Fox and colleagues recently reported that DOI and the conformationally restricted 5-HT 2A agonist TCB-2 have no effect on locomotor activity in C57BL/6J mice (Fox et al, 2010). Given these discrepant findings, we tested a larger series of phenylalkylamine hallucinogens and related substances (Figure 1) in the BPM to determine whether those compounds increase locomotor activity by activating the 5-HT 2A receptor.…”

Section: Introductionmentioning

confidence: 99%

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Role of the 5-HT2A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice

2013

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The 5-HT2A receptor mediates the effects of serotonergic hallucinogens and may play a role in the pathophysiology of certain psychiatric disorders, including schizophrenia. Given these findings, there is a need for animal models to assess the behavioral effects of 5-HT2A receptor activation. Our previous studies demonstrated that the phenylalkylamine hallucinogen and 5-HT2A/2C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) produces dose-dependent effects on locomotor activity in C57BL/6J mice, increasing activity at low to moderate doses and reducing activity at high doses. DOI did not increase locomotor activity in 5-HT2A knockout mice, indicating the effect is a consequence of 5-HT2A receptor activation. Here, we tested a series of phenylalkylamine hallucinogens in C57BL/6J mice using the Behavioral Pattern Monitor (BPM) to determine whether these compounds increase locomotor activity by activating the 5-HT2A receptor. Low doses of mescaline, 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-propylamphetamine (DOPR), 2,4,5-trimethoxyamphetamine (TMA-2), and the conformationally restricted phenethylamine (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine (TCB-2) increased locomotor activity. By contrast, the non-hallucinogenic phenylalkylamine 2,5-dimethoxy-4-tert-butylamphetamine (DOTB) did not alter locomotor activity at any dose tested (0.1-10 mg/kg i.p.). The selective 5-HT2A antagonist M100907 blocked the locomotor hyperactivity induced by mescaline and TCB-2. Similarly, mescaline and TCB-2 did not increase locomotor activity in 5-HT2A knockout mice. These results confirm that phenylalkylamine hallucinogens increase locomotor activity in mice and demonstrate that this effect is mediated by 5-HT2A receptor activation. Thus, locomotor hyperactivity in mice can be used to assess phenylalkylamines for 5-HT2A agonist activity and hallucinogen-like behavioral effects. These studies provide additional support for the link between 5-HT2A activation and hallucinogenesis.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

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Role of the 5-HT2A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice

2013

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“…Phenylalkylamines, including DOI, mescaline, and TCB-2, inhibit investigatory behavior and alter locomotor activity in a dose-dependent manner, increasing activity at low to moderate doses and reducing activity at high doses (Halberstadt et al, 2009, 2013). Other groups have reported similar findings with DOM and DOI in mice (Yamamoto and Ueki, 1975; Darmani, 1996; Brookshire and Jones, 2009; Carlsson et al, 2011). The increase in locomotor activity induced by 1 mg/kg DOI, 25 mg/kg mescaline, or 3 mg/kg TCB-2 is blocked by low doses of M100907 and is absent in 5-HT 2A knockout mice.…”

Section: Involvement Of the 5-ht2a Receptor In Hallucinogen Effectssupporting

confidence: 79%

Recent advances in the neuropsychopharmacology of serotonergic hallucinogens

Halberstadt

2015

Behavioural Brain Research

241

203

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Serotonergic hallucinogens, such as (+)-lysergic acid diethylamide, psilocybin, and mescaline, are somewhat enigmatic substances. Although these drugs are derived from multiple chemical families, they all produce remarkably similar effects in animals and humans, and they show cross-tolerance. This article reviews the evidence demonstrating the serotonin 5-HT2A receptor is the primary site of hallucinogen action. The 5-HT2A receptor is responsible for mediating the effects of hallucinogens in human subjects, as well as in animal behavioral paradigms such as drug discrimination, head twitch response, prepulse inhibition of startle, exploratory behavior, and interval timing. Many recent clinical trials have yielded important new findings regarding the psychopharmacology of these substances. Furthermore, the use of modern imaging and electrophysiological techniques is beginning to help unravel how hallucinogens work in the brain. Evidence is also emerging that hallucinogens may possess therapeutic efficacy.

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“…In addition to decreased locomotion and stereotypy, we demonstration a cocaine induced increase in vertical activity in cocaine self administering animals. Serotonin levels are inversely related to vertical activity (Brookshire and Jones, 2009); thus, it is possible that the serotonin system may also be affected by cocaine self-administration. Studies of whole brain functional activity after this self-administration paradigm have observed reduced dorsal raphe activity (Calipari et al, 2013c).…”

Section: Discussionmentioning

confidence: 99%

Extended access of cocaine self‐administration results in tolerance to the dopamine‐elevating and locomotor‐stimulating effects of cocaine

Calipari

Ferris

Jones

2013

Journal of Neurochemistry

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Tolerance to the neurochemical and psychoactive effects of cocaine after repeated use is a hallmark of cocaine addiction in humans. However, comprehensive studies on tolerance to the behavioral, psychoactive, and neurochemical effects of cocaine following contingent administration in rodents are lacking. We outlined the consequences of extended access cocaine self-administration as it related to tolerance to the psychomotor activating, dopamine (DA) elevating, and DA transporter (DAT) inhibiting effects of cocaine. Cocaine self-administration (1.5 mg/kg/inj; 40 inj; 5 days), which resulted in escalation of first hour intake, caused reductions in evoked DA release and reduced maximal rates of uptake through the DAT as measured by slice voltammetry in the nucleus accumbens core. Further, we report reductions in cocaine-induced uptake inhibition as measured by fast scan cyclic voltammetry, and a corresponding increase in the dose of cocaine required for 50% inhibition of DA uptake (Ki) at the DAT. Cocaine tolerance at the DAT translated to reductions in cocaine-induced DA overflow as measured by microdialysis. Additionally, cocaine-induced elevations in locomotor activity and stereotypy were reduced, while rearing behavior was enhanced in animals with a history of cocaine self-administration. Here we demonstrate both neurochemical and behavioral cocaine tolerance in an extended-access rodent model of cocaine abuse, which allows for a better understanding of the neurochemical and psychomotor tolerance that develops to cocaine in human addicts.

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Direct and indirect 5-HT receptor agonists produce gender-specific effects on locomotor and vertical activities in C57 BL/6J mice

Cited by 36 publications

References 48 publications

Role of the 5-HT2A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice

Role of the 5-HT2A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice

Recent advances in the neuropsychopharmacology of serotonergic hallucinogens

Extended access of cocaine self‐administration results in tolerance to the dopamine‐elevating and locomotor‐stimulating effects of cocaine

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