Effects of the selective 5-HT receptor agonists 8-OHDPAT and DOI on behavior and brain biogenic amines of rats

Gaggi, R; Dall’Olio, Rossella; Roncada, Paola

doi:10.1016/s0306-3623(96)00240-6

Cited by 25 publications

(9 citation statements)

References 18 publications

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“…Thus, the relatively weaker effect on HFO power, in comparison to NMDAR antagonists, is unlikely to be related to the doses we used. Indeed, at the medium and high doses of LSD and DOI, we observed clear classical behavioural effects such as wet-dog shakes and postural changes, as reported by others (Gaggi et al 1997). Even at the lowest dose, we found a clear reduction in gamma power (see Figs.…”

Section: Discussionsupporting

confidence: 88%

“…5). The maximal doses of LSD and DOI used in this study were towards the top end of those typically used by other groups (Bishop et al 2004; Erdtmann-Vourliotis et al 1999; Gaggi et al 1997; Nielsen and Scheel-Kruger 1986). Thus, the relatively weaker effect on HFO power, in comparison to NMDAR antagonists, is unlikely to be related to the doses we used.…”

Section: Discussionmentioning

confidence: 90%

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Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens

et al. 2013

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RationaleThe nucleus accumbens (NAc) is a site critical for the actions of many drugs of abuse. Psychoactive compounds, such as N-methyl-d-aspartate receptor (NMDAR) antagonists, modify gamma (40-90) and high frequency oscillations (HFO, 130–180 Hz) in local field potentials (LFPs) recorded in the NAc. Lysergic acid diethylamide (LSD) and 2,5-dimethoxy-4-iodoamphetamine (DOI) are serotonergic hallucinogens and activation of 5HT2A receptors likely underlies their hallucinogenic effects. Whether these compounds can also modulate LFP oscillations in the NAc is unclear.ObjectiveThis study aims to examine the effect of serotonergic hallucinogens on gamma and HFO recorded in the NAc and to test whether 5HT2A receptors mediate the effects observed.MethodsLFPs were recorded from the NAc of freely moving rats. Drugs were administered intraperitoneally.ResultsLSD (0.03–0.3 mg/kg) and DOI (0.5–2.0 mg/kg) increased the power and reduced the frequency of HFO. In contrast, the hallucinogens produced a robust reduction in the power of low (40–60 Hz), but not high gamma oscillations (70–90 Hz). MDL 11939 (1.0 mg/kg), a 5HT2A receptor antagonist, fully reversed the changes induced by DOI on HFO but only partially for the low gamma band. Equivalent increases in HFO power were observed after TCB-2 (5HT2A receptor agonist, 0.1–1.5 mg/kg), but not CP 809101 (5H2C receptor agonist, 0.1–3 mg/kg). Notably, hallucinogen-induced increases in HFO power were smaller than those produced by ketamine (25 mg/kg).ConclusionsSerotonergic hallucinogen-induced changes in HFO and gamma are mediated, at least in part, by stimulation of 5HT2A receptors. Comparison of the oscillatory changes produced by serotonergic hallucinogens and NMDAR antagonists are also discussed.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-013-3057-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 90%

Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens

et al. 2013

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“…This suggests that both antidepressants act in the FPT when retested via other mechanisms, or that the activation of 5-HT 2A receptors by these antidepressants is not sufficient enough to oppose fear potentiation. Although the study of Bortolozzi et al (2003) has shown that the application of the 5-HT 2A/2C agonist DOI by reverse dialysis in the medial prefrontal cortex of mice doubled the local release of 5-hydroxytryptamine, several studies have revealed that the DOI seems to increase dopamine and GABA levels rather than 5-HT levels (Abi-saab et al 1999;Gaggi et al 1997;Gobert and Millan 1999;Ichikawa et al 2001a,b;Pehek et al 2001). DOI, via the 5-HT 2A and DA receptors, may regulate GABA release and possibly in this way produce its anxiolytic-like effects in naive mice (Nic Dhonnchadha et al 2003b).…”

Section: Discussionmentioning

confidence: 99%

The four-plates test–retest paradigm to discriminate anxiolytic effects

Ripoll¹,

Dhonnchadha²,

Sébille

et al. 2005

Psychopharmacology

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“…Thus in rats, F15599 exhibited little propensity to elicit forepaw treading or flat body posture, which are elements of 5-HT behavioral syndrome commonly observed with 5-HT 1A receptor agonists [124,125]. F15599 only elicited these responses at doses that were 30-60-fold higher than those that suppress immobility in the FST [99].…”

Section: Review Newman-tancredimentioning

confidence: 93%

Biased agonism at serotonin 5-HT_1Areceptors: preferential postsynaptic activity for improved therapy of CNS disorders

Newman‐Tancredi¹

2011

Neuropsychiatry

106

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Practice pointsSerotonin or 5-hydroxytryptamine (5-HT) 1A receptors are attractive targets for pharmacotherapy of pathologies associated with dysfunctional serotonergic neurotransmission, including anxiety, depression, Parkinson's disease, pain and schizophrenia. 5-HT 1A receptors are expressed both as presynaptic autoreceptors on serotonergic cell bodies in the raphe and as postsynaptic heteroreceptors in multiple brain regions including the cortex, hippocampus, septum and hypothalamus.The signaling cascades elicited by 5-HT 1A receptor activation differ between brain regions: different G-protein subtypes, different second messengers and different neurochemical read-outs.The concept of 'biased agonism' or 'functional selectivity' asserts that agonists can preferentially direct receptor signaling to specific intracellular responses. This opens the possibility of targeting receptors in specific cellular environments or brain regions.F15599 is a selective 5-HT 1A receptor agonist that exhibits biased agonism, preferentially activating Gai versus Gao G-protein subtypes. F15599 preferentially activates ERK1/2 phosphorylation more than G-protein, receptor internalization or adenylyl cyclase inhibition.F15599 stimulates rat medial prefrontal cortex pyramidal neuron electrical activity and dopamine release (controlled by postsynaptic 5-HT 1A receptors) at low doses that do not inhibit raphe serotonergic neuron electrical activity or hippocampal 5-HT release (controlled by presynaptic 5-HT 1A receptors).F15599 preferentially stimulates c-Fos expression and ERK1/2 phosphorylation in rat prefrontal cortex, with less pronounced effects in the raphe. This preferential postsynaptic activity is not observed with other 5-HT 1A agonists.In rats F15599 exhibits potent antidepressant-like activity in the forced swim test, inhibits stress-induced ultrasonic vocalization and attenuates phencyclidine-induced cognitive impairments in reversal learning, in novel object recognition and in a hole-board test.At 'antidepressant' doses in rats, F15599 does not induce serotonin syndrome, does not disrupt attentional performance, does not impair working memory and does not inhibit prepulse inhibition of startle response.For reprint orders, please contact: reprints@futuremedicine.com

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Effects of the selective 5-HT receptor agonists 8-OHDPAT and DOI on behavior and brain biogenic amines of rats

Cited by 25 publications

References 18 publications

Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens

Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens

The four-plates test–retest paradigm to discriminate anxiolytic effects

Biased agonism at serotonin 5-HT_1Areceptors: preferential postsynaptic activity for improved therapy of CNS disorders

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Effects of the selective 5-HT receptor agonists 8-OHDPAT and DOI on behavior and brain biogenic amines of rats

Cited by 25 publications

References 18 publications

Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens

Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens

The four-plates test–retest paradigm to discriminate anxiolytic effects

Biased agonism at serotonin 5-HT1Areceptors: preferential postsynaptic activity for improved therapy of CNS disorders

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Biased agonism at serotonin 5-HT_1Areceptors: preferential postsynaptic activity for improved therapy of CNS disorders