Behavioural evidence for functional interactions between 5‐HT‐receptor subtypes in rats and mice

Berendsen, Hemmie H.G.; Broekkamp, C.L.E.

doi:10.1111/j.1476-5381.1990.tb14138.x

Cited by 128 publications

(57 citation statements)

References 25 publications

(38 reference statements)

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“…They are highly colocalized (80%) in pyramidal neurons of the PFC (Santana et al, 2004) and electrophysiological studies have shown that M100907 potentiate 8-OH-DPAT suppression on firing rate (Ashby et al, 1994). In addition, 5-HT 2A receptor antagonists ICI 180,809 and ritanserin potentiate the 5-HT syndrome produced by 8-OH-DPAT Sharp et al, 1990) whereas 8-OH-DPAT inhibits head twitching behavior induced by systemic DOI (Berendsen and Broekkamp, 1990;Darmani et al, 1990;Dursun and Handley, 1993) or microinjection into the mPFC of (À) DOB, a congener of DOI and a 5-HT 2A/2C receptors agonist (Granhoff et al, 1992). Clearly, the opposition between the two 5-HT receptor subtypes suggests that the improvement produced by M100907 and 8-OH-DPAT on CPP-induced accuracy deficit may result from a functionally antagonistic activity of these receptors on a common intracellular mechanism.…”

Section: Discussionmentioning

confidence: 99%

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

169

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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Section: Discussionmentioning

confidence: 99%

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

169

158

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“…19, NO. 5 ( Arnt and Hyttel 1989;Berendsen and Broekkamp 1990) and attenuated by co-administration of the 5-HT 2C receptor agonists MK 212 and mCPP (Berendsen and Broekkamp). An alternative explanation for the modest effect of chronic DOI treatment on 8-OH-DPAT-induced hypothermia and forepaw treading may be the partial agonist activity of DOI.…”

Section: Discussionmentioning

confidence: 99%

“…DOI, with equal affinity for members of the 5-HT 2 receptor family, may activate 5-HT 2 receptors that have opposing effects on these 5-HT 1A receptor-mediated behaviors. For example, forepaw treading in rats induced by 8-OH-DPAT is potentiated by co-administration of DOI (Arnt and Hyttel 1989;Berendsen and Broekkamp 1990) and attenuated by co-administration of the 5-HT 2C receptor agonists MK 212 and mCPP (Berendsen and Broekkamp). An alternative explanation for the modest effect of chronic DOI treatment on 8-OH-DPAT-induced hypothermia and forepaw treading may be the partial agonist activity of DOI.…”

Section: Discussionmentioning

confidence: 99%

“…For example, 5-HT 2A receptor-mediated head shake behavior in rats (Schreiber et al 1995) elicited by the 5-HT 2 receptor agonist DOI is attenuated by co-administration of 5-HT 1A receptor agonists (Arnt and Hyttel 1989;Yocca et al 1990). Forepaw treading induced by acute injection of the 5-HT 1A receptor agonist 8-OH-DPAT is potentiated by co-administration of DOI (Arnt and Hyttel;Berendsen and Broekkamp 1990) and attenuated by coadministration of the 5-HT 2C receptor agonists MK 212 and mCPP (Berendsen and Broekkamp). 5-HT 2 receptor antagonists have also been reported to increase 8-OH-DPAT-induced forepaw treading (Backus et al 1990).…”

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Effect of Chronic Serotonin-2 Receptor Agonist or Antagonist Administration on Serotonin-1A Receptor Sensitivity

Hensler

Truett

1998

Neuropsychopharmacology

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We have investigated the effect of 5-HT 2 receptor agonist or antagonist administration on postsynaptic 5-HT 1A receptor sensitivity assessed by two behavioral measures, reciprocal forepaw treading or hypothermia induced by acute injection of the 5-HT 1A receptor agonist 8-OH-DPAT. The effectiveness of these drug treatments to downregulate 5-HT 2A receptors was confirmed by measuring the binding of [ 3 H]-ketanserin in cortical homogenates, because all of these drug treatments have been shown to result in the downregulation of 5-HTOf some 14 subtypes of receptor for the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) (see Hoyer et al. 1994), a tremendous amount of attention has been focused on the serotonin 1A (5-HT 1A ) receptor subtype. Drugs that act as agonists at this receptor have proved useful clinically as antidepressants (see Murphy et al. 1995) and anxiolytics (Coplan et al. 1995). The unique distribution of this serotonin receptor subtype in brain is consistent with its potential involvement in cognitive or integrative functions, as well as in emotional states. In terminal field areas of serotonergic innervation, the 5-HT 1A receptor is located postsynaptically and is present in high density in cortical and limbic structures (i.e., hippocampus, entorhinal cortex, septum, amygdala, frontal cortex) (Vergé et al. 1986;Hensler et al. 1991;Khawaja 1995). The 5-HT 1A receptor is also found in high density in serotonin cell body areas, such as the dorsal and median raphé, where it is believed to function as the somatodendritic autoreceptor modulating the activity of serotonergic neurons (see Aghajanian et al. 1990).The sensitivity of behavioral (Goodwin et al. 1987;Hensler et al. 1991;Wieland et al. 1993;Maj et al. 1996) and electrophysiological (Blier and deMontigny 1983, Received June 16, 1997; revised December 15, 1997; accepted February 16, 1998. N EUROPSYCHOPHARMACOLOGY 1998 -VOL . 19 , NO . 5 Modulation of 5-HT 1A Receptor Sensitivity 355 1985 responses mediated by the 5-HT 1A receptor is decreased after chronic administration of 5-HT 1A receptor agonists or antidepressants drugs. The desensitization of 5-HT 1A receptor-mediated responses has also been reported to occur after acute or short-term agonist administration (Kennett et al. 1987;Larsson et al. 1990). Although some investigators have reported changes in 5-HT 1A receptor number following agonist or antidepressant treatments (Welner et al. 1989;Fanelli and McMonagle-Strucko 1992), in many cases desensitization of 5-HT 1A receptor-mediated responses has not been found to be accompanied by a decrease 5-HT 1A receptor number (Larsson et al. 1990;Schecter et al. 1990;Hensler et al. 1991;Wieland et al. 1993). Changes in 5-HT 1A receptor second messenger function have not been consistently reported to follow administration of antidepressants or 5-HT 1A receptor agonists (Sleight et al. 1988;Varrault et al. 1991;Newman et al. 1992).Interactions between serotonin receptor subtypes have been observed in behavioral studies. For example, 5...

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“…For example, both flattened body posture and hypothermia, two behaviors elicited by 5-HT 1A receptor agonists, are reduced when 5-HT 2 receptor agonists are administered together with 5-HT 2 receptor agonists [2,5]. Consistent with our findings that VMN infusion with DOI prevented the lordosis-inhibiting effect of 8-OH-DPAT [40], addition of the 5-HT 2 receptor agonist, DOI, to tissue slices of the VMN attenuated the inhibitory effects of 5-HT 1A receptor agonists on neuronal firing [19].…”

Section: Introductionmentioning

confidence: 99%

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Selvamani

Lincoln

Uphouse

2007

Behavioural Brain Research

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Ovariectomized rats with bilateral cannulae near the ventromedial nucleus of the hypothalamus were hormonally primed with 10μg estradiol benzoate and 500μg progesterone. Sexually receptive females were infused bilaterally with 200 ng of the 5-HT 1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), or with a combination of 200 ng 8-OH-DPAT and 2000 ng of the 5-HT 2 receptor agonist, (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl (DOI). 8-OH-DPAT inhibited lordosis behavior and DOI reduced this inhibition. However, if females were preinfused with the PKC inhibitor, bisindolymaleimide I hydrochloride (BIM), DOI's effect was eliminated. BIM's attenuation of the effects of DOI was time-dependent. When BIM was infused 90 min, but not 30 min, before the 5-HT receptor agonists, BIM eliminated DOI's protection against the lordosisinhibiting effects of 8-OH-DPAT. A concentration of BIM as low as 10 −5 nmol in a 0.5μl infusion volume was effective and there was little evidence of dose responsivity between 10 −5 and 10 −1 nmol of BIM. In contrast, prior infusion with vehicle or with 10 −7 nmol BIM had no impact on the female's response to the 5-HT receptor agonists. These findings allow the suggestion that DOI's ability to increase PKC may be responsible for attenuation of the effects of 8-OH-DPAT on lordosis behavior. KeywordsPKC inhibitor; 5-HT 1A receptors; 5-HT 2 receptors; ovariectomized; sexual behavior IntroductionWithin the ventromedial nucleus of the hypothalamus (VMN), serotonin (5-HT) modulates female rat sexual behavior by acting on multiple 5-HT receptors [39]. Lordosis behavior, a supraspinal estrogen-dependent reflex of sexually receptive females [29], is inhibited by 5-HT 1A receptor agonists and facilitated by 5-HT 2 receptor agonists and their coactivation attenuates the lordosis-inhibitory effects of 5-HT 1A receptor agonists [39]. We have proposed that this 5-HT 1A /5-HT 2 receptor interaction enables the female to fine-tune her behavior so that it is most adaptive to environmental conditions [42]. However, the mechanisms for this interaction are not known.

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Behavioural evidence for functional interactions between 5‐HT‐receptor subtypes in rats and mice

Cited by 128 publications

References 25 publications

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

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

Effect of Chronic Serotonin-2 Receptor Agonist or Antagonist Administration on Serotonin-1A Receptor Sensitivity

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

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