The 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism

Higgins, Guy A.; Enderlin, M; Haman, Marie; Fletcher, Paul

doi:10.1007/s00213-003-1549-0

Cited by 169 publications

(172 citation statements)

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“…M100907 also reduces the elevated locomotor activity (Gleason and Shannon, 1997;Martin et al, 1997), forced swim immobility (Corbett et al, 1999), and deficit in prepulse inhibition (Varty et al, 1999) induced by NMDA receptor antagonists. In rats performing a 5-CSRT task, M100907 improved attentional performance (Winstanley et al, 2003;Passetti et al, 2003a) and reversed the deficit in inhibitory response control induced by systemic administration of the NMDA receptor antagonists, dizocilpine and Ro 63-1908 (Higgins et al, 2004).…”

Section: Introductionmentioning

confidence: 94%

The Serotonin 5-HT2A Receptors Antagonist M100907 Prevents Impairment in Attentional Performance by NMDA Receptor Blockade in the Rat Prefrontal Cortex

Carli

Baviera

Invernizzi

et al. 2004

Neuropsychopharmacol

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We investigated whether 5-HT 2A receptors contribute to the control of attentional performance by glutamate NMDA receptor mechanisms in the medial prefrontal cortex (mPFC). We examined the effects of NMDA receptor blockade in the mPFC on attentional performance by infusing a competitive glutamate NMDA receptor antagonist, 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) into the mPFC of rats performing a task of divided and sustained visual attention. The five-choice serial reaction time task provides indices of attentional functioning (% correct responses), executive control (measured by anticipatory and perseverative responses) and speed. A dose of 10 ng CPP injected bilaterally into the mPFC increased anticipatory and perseverative responding; 50 ng reduced accuracy. Increasing the stimulus duration alleviated the CPP-induced accuracy deficit but did not reduce its effects on anticipatory and perseverative responses. CPP at 50 ng caused motor hyperactivity whereas lower doses had no effect., a 5-HT 2A receptor antagonist, injected subcutaneously at 10 and 40 mg/kg, had no effect on accuracy but dose dependently reversed the impairment induced by 50 ng CPP. Both doses of M100907 completely abolished CPP-induced anticipatory but not perseverative over-responding. At the dose of 40 mg/kg M100907 reversed CPPinduced motor hyperactivity. This study provides evidence that the prefronto-cortical glutamate NMDA system may make an important contribution to the control of attention and executive functions. It also indicates that 5-HT 2A receptors may serve to optimize attentional selectivity and improve some aspects of executive control.

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Section: Introductionmentioning

confidence: 94%

The Serotonin 5-HT2A Receptors Antagonist M100907 Prevents Impairment in Attentional Performance by NMDA Receptor Blockade in the Rat Prefrontal Cortex

Carli

Baviera

Invernizzi

et al. 2004

Neuropsychopharmacol

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“…In fact, impulsivity in a 5-CSRT task as measured by anticipatory responses was associated with high 5-HT turnover (Puumala and Sirvio, 1998) and release in the mPFC (Dalley et al, 2002). Stimulation of 5-HT 2A receptors by a variety of 5-HT 2A agonists increased whereas blockade of 5-HT 2A receptors (by antagonists) reduced anticipatory responses (Higgins et al, 2003b;Koskinen et al, 2000;Mirjana et al, 2004;Passetti et al, 2003b;Winstanley et al, 2003).…”

Section: Discussionmentioning

confidence: 95%

“…While activation of 5-HT 1A and 5-HT 2A receptors in the mPFC has opposite effects on attentional functioning (Winstanley et al, 2003), the 5-HT 2A but not 5-HT 1A receptors appear particularly involved in processes controlling response inhibition (Koskinen et al, 2000;Winstanley et al, 2003). In addition, a selective antagonist at 5-HT 2A receptors, M100907, reverses the effects of systemic or intra-mPFC NMDA antagonists on attentional functioning and some aspects of executive function Higgins et al, 2003b).…”

Section: Introductionmentioning

confidence: 99%

“…The five-choice serial reaction time (5-CSRT) task used to assess attentional and executive functions in rodents is functionally analogous to the continuous performance test in humans Higgins et al, 2003b;Robbins, 2002) and schizophrenic subjects reliably show impairments in the task, compared to controls (Kurtz et al, 2001;Orzack and Kornetsky, 1966). The 5-CSRT task taxes attentional capacity, as indicated by accuracy of correctly reporting the location of a brief visual stimulus, in addition to inhibitory response control related to executive attentional processes that permit accurate response selection in the face of distraction and interference (Robbins, 1998;Shallice, 1982).…”

Section: Introductionmentioning

confidence: 99%

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Dissociable Contribution of 5-HT1A and 5-HT2A Receptors in the Medial Prefrontal Cortex to Different Aspects of Executive Control such as Impulsivity and Compulsive Perseveration in Rats

Carli

Baviera

Invernizzi

et al. 2005

Neuropsychopharmacol

170

158

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Serotonin (5-HT) receptors are increasingly recognized as major targets for cognitive enhancement in schizophrenia. Several lines of evidence suggest a pathophysiological role for glutamate NMDA receptors in the prefrontal cortex in schizophrenia and associated disorders in attention and executive functioning. We investigated how the interactions between 5-HT 1A and 5-HT 2A and glutamate NMDA receptor mechanisms in the medial prefrontal cortex (mPFC) contribute to the control of different aspects of attentional performance. Rats were trained on a five-choice serial reaction time (5-CSRT) task, which provides indices of attentional functioning (percentage of correct responses), executive control (measured by anticipatory and perseverative responses), and speed. The competitive NMDA receptor antagonist CPP (50 ng/side) was infused directly into the mPFC 5 min after infusion of either 8-OH-DPAT (30 and 100 ng/side) or M100907 (100 and 300 ng/side) into the same brain area. Impairments in attentional functioning induced by CPP were completely abolished by both doses of 8-OH-DPAT or M100907. In addition, M100907 abolished the CPP-induced anticipatory responding but had no effects on perseverative over-responding, while 8-OH-DPAT reduced the perseverative over-responding but had no effects on anticipatory responding induced by CPP. The selective 5-HT 1A receptor antagonist WAY100635 (30 ng/side) antagonized the effects of 8-OH-DPAT (100 ng/side). 8-OH-DPAT at 30 ng/side reduced the latency of correct responses in controls and CPPinjected rats and lowered the percentage of omissions in CPP-injected rats. The data show that 5-HT 1A and 5-HT 2A receptors in the mPFC exert opposing actions on attentional functioning and demonstrate a dissociable contribution of 5-HT 1A and 5-HT 2A receptors in the mPFC to different aspects of executive control such as impulsivity and compulsive perseveration.

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“…Interestingly, recent studies show that impulsive-type behaviours (such as hyperlocomotion and stereotypy) induced by blockade of NMDA receptors can be attenuated by administration of 5-HT 2A antagonists [24,76], suggesting a possible use of 5-HT 2A receptor antagonists to normalise NMDA receptor hypofunction.…”

Section: Role In Motor Controlmentioning

confidence: 99%

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

Ciranna

2006

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170

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Abstract:The neurotransmitter serotonin (5-HT), widely distributed in the central nervous system (CNS), is involved in a large variety of physiological functions. In several brain regions 5-HT is diffusely released by volume transmission and behaves as a neuromodulator rather than as a "classical" neurotransmitter. In some cases 5-HT is co-localized in the same nerve terminal with other neurotransmitters and reciprocal interactions take place. This review will focus on the modulatory action of 5-HT on the effects of glutamate and -amino-butyric acid (GABA), which are the principal neurotransmitters mediating respectively excitatory and inhibitory signals in the CNS. Examples of interaction at preand/or post-synaptic levels will be illustrated, as well as the receptors involved and their mechanisms of action. Finally, the physiological meaning of neuromodulatory effects of 5-HT will be briefly discussed with respect to pathologies deriving from malfunctioning of serotonin system.

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The 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism

Cited by 169 publications

References 58 publications

The Serotonin 5-HT2A Receptors Antagonist M100907 Prevents Impairment in Attentional Performance by NMDA Receptor Blockade in the Rat Prefrontal Cortex

The Serotonin 5-HT2A Receptors Antagonist M100907 Prevents Impairment in Attentional Performance by NMDA Receptor Blockade in the Rat Prefrontal Cortex

Dissociable Contribution of 5-HT1A and 5-HT2A Receptors in the Medial Prefrontal Cortex to Different Aspects of Executive Control such as Impulsivity and Compulsive Perseveration in Rats

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

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