Selective visualization of rat brain 5-HT2A receptors by autoradiography with [3H]MDL 100,907

López-Giménez, Juan F.; Mengod, Guadalupe; Palacios, J.M.; Vilaró, M. Teresa

doi:10.1007/pl00005075

Cited by 181 publications

(136 citation statements)

References 31 publications

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“…Eberle-Wang et al (1997) demonstrated the presence of 5-HT 2C mRNA within inhibitory GABAergic interneurons making direct synaptic contact with dopaminergic cell bodies in both the VTA and substantia nigra. The 5-HT 2A receptors are particularly prominent in cortical areas but are also found in DA-rich areas such as the striatum, substantia nigra, and VTA (Pompeiano et al, 1994;Lopez-Gimenez et al, 1997;Doherty and Pickel, 2000).…”

Section: Experiments 2: Effects Of Sb 242084 On Reversal Learningmentioning

confidence: 99%

Dissociable Effects of Selective 5-HT2A and 5-HT2C Receptor Antagonists on Serial Spatial Reversal Learning in Rats

Boulougouris

Glennon

Robbins

2007

Neuropsychopharmacol

199

183

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Serotonin (5-hydroxytryptamine, or 5-HT) is strongly implicated in the ability to shift behavior in response to changing stimulus-reward contingencies. However, there is little information on the contribution of different 5-HT receptors in reversal learning. Thus, we investigated the effects of systemic administration of the 5-HT 2A antagonist M100907 (0, 0.01, 0.03, and 0.1 mg/kg, i.p.) and the 5-HT 2C antagonist SB 242084 (0, 0.1, 0.3, and 1.0 mg/kg, i.p.) on the performance of an instrumental two-lever spatial discrimination and serial spatial reversal learning task, where both levers were presented and only one was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a series of within-session reversals was presented. Neither M100907 nor SB 242084 altered performance during spatial discrimination and retention of the previously reinforced contingencies. M100907 significantly impaired reversal learning by increasing both trials to criterion (only at the highest dose) and incorrect responses to criterion in Reversal 1, a pattern of behavior manifested as increased perseverative responding on the previously reinforced lever. In contrast, SB 242084 improved reversal learning by decreasing trials and incorrect responses to criterion in Reversal 1, with significantly fewer perseverative responses. These data support the view that 5-HT 2A and 5-HT 2C receptors have distinct roles in cognitive flexibility and response inhibition. The improved performance in reversal learning observed following 5-HT 2C receptor antagonism suggests these receptors may offer the potential for therapeutic advances in a number of neuropsychiatric disorders where cognitive deficits are a feature, including obsessive-compulsive disorder.

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Section: Experiments 2: Effects Of Sb 242084 On Reversal Learningmentioning

confidence: 99%

Dissociable Effects of Selective 5-HT2A and 5-HT2C Receptor Antagonists on Serial Spatial Reversal Learning in Rats

Boulougouris

Glennon

Robbins

2007

Neuropsychopharmacol

199

183

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“…The 5-HT 2A and 5-HT 2C receptors were hypothesized to be particularly important because of the moderate to dense localization of both transcript and protein for these receptors in SN and VTA as well as DA terminal regions of rat forebrain (Abramowski et al 1995;Lopez-Gimenez et al 1997;Pompeiano et al 1994). Antagonism of 5-HT 2A (De Deurwaerdere and Spampinato 1999;Lucas and Spampinato 2000) and 5-HT 2C receptors (De Deurwaerdere and Spampinato 1999; Di Giovanni et al 1999; Di Matteo et al 1998;Lucas and Spampinato 2000) has been shown to influence DA function in areas of brain (e.g., NAc and striatum) thought to be important in motor activation, motivation, and reward.…”

Section: Dysfunction Of Monoamine Neurotransmission Seems To Contribumentioning

confidence: 99%

Role of 5-HT2A and 5-HT2B/2C Receptors in the Behavioral Interactions Between Serotonin and Catecholamine Reuptake Inhibitors

McMahon

2001

Neuropsychopharmacology

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Dysfunction of monoamine neurotransmission seems to contribute to such pathopsychological states as depression, schizophrenia, and drug abuse. The present study examined the effects of the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) and antidepressant fluvoxamine on locomotor activity in rats following administration of the catecholamine reuptake inhibitor mazindol. Mazindol (1 mg/kg) did not alter locomotor activity; whereas, fluvoxamine (20 mg/kg) given alone induced a brief period of hypomotility. Hyperactivity was elicited in a doserelated manner when fluvoxamine (5-20 mg/kg) was combined with mazindol (1 mg/kg). The hyperactivity elicited by fluvoxamine (20 mg/kg) Several lines of evidence suggest that dopamine (DA) and serotonin (5-hydroxy tryptamine; 5-HT) interact in the central nervous system and that dysfunction of these neurotransmitters may contribute to such pathopsychological states as depression, schizophrenia, and drug abuse (Kahn and Davidson 1993;Kosten et al. 1998). The 5-HT-containing cell bodies of the dorsal raphe nucleus project to DA cell bodies of the ventral tegmental area (VTA) and substantia nigra (SN), and to their terminal fields in the prefrontal cortex (PFC), nucleus accumbens (NAc), and striatum (Hervé et al. 1987;Steinbush et al. 1981; Van der Kooy and Hattori 1980). The precise nature of the interaction between 5-HT and DA has been difficult to elucidate, with both inhibitory and excitatory roles for 5-HT identified with respect to the neural activity of DA neurons and the release of DA. For example, electrophysiological studies in vivo suggest an inhibitory influence of 5-HT on DA cell bodies of the VTA and SN (Prisco et al. 1994;Kelland et al. 1990), and 5-HT inhibits DA release from striatal slices (Ennis et al. 1981;Westfall and Tittermary 1982). On the other hand, in vivo microdialysis studies consistently demonstrate that local infusion of 5-HT increases DA efflux in the PFC, NAc, and striatum (Benloucif et al. NO . 3 1993; Gobert and Millan 1999; Iyer and Bradberry 1996;Parsons and Justice 1993), possibly through stimulation of one or more of the 14 5-HT receptor subtypes characterized to date (Barnes and Sharp 1999).The behavioral importance of 5-HT and DA interactions has been difficult to define. Much of this research has focused on modifications of behaviors evoked by enhanced DA neurotransmission consequent to psychostimulant administration. In early studies, reductions and enhancements of the locomotor stimulatory effects of cocaine (Scheel-Kruger et al. 1976) and amphetamine (Geyer et al. 1976) were reported following increased 5-HT synthesis or depletion of 5-HT, respectively. These and similar findings generated the hypothesis that 5-HT plays an inhibitory role in DA-mediated behavior. On the other hand, systemic administration of selective serotonin reuptake inhibitors (SSRIs) potentiated hyperactivity induced by amphetamine or cocaine in rats (Herges and Taylor 1998;Sills et al. 1999aSills et al. , 1999b, but not in mice (Arn...

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“…Similarly, M100907, a selective 5HT 2A receptor antagonist, but not the 5HT 2C receptor antagonist SB 200,646, blocked the discriminative stimulus effects of phenethylamine hallucinogens (Schreiber et al, 1994;Eckler et al, 2004) Although 5-HT 2A receptors play a prominent role in mediating the stimulus effects of hallucinogenic drugs, the anatomical location of the relevant receptors is unclear. 5-HT 2A receptors are distributed throughout the brain, but are found in high density in various cortical regions (especially the frontal cortex), caudate nucleus, nucleus accumbens, olfactory nucleus, and claustrum (Pazos et al, 1985;Appel et al, 1990;López-Giménez et al, 1997). The objective of the present study was to identify the neuroanatomical location of the 5-HT 2A receptors that may be responsible for mediating the stimulus effects of DOM, a 5-HT 2A receptor agonist with hallucinogenic activity, in the rat.…”

Section: Introductionmentioning

confidence: 99%

Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas

Doat-Meyerhoefer

Hard

Winter

et al. 2005

Pharmacology Biochemistry and Behavior

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Activation of 5-HT 2A receptors has been shown to be an essential component of the discriminative stimulus effects of indoleamine and phenethylamine hallucinogens. The objective of the present study was to determine the neuroanatomical location of the 5HT 2A receptors which may be responsible for the stimulus effects of the phenethylamine hallucinogen [−]2,5-dimethoxy-4-methylamphetamine (DOM). It was hypothesized that brain areas containing altered 5-HT 2A receptor expression in the context of a similar alteration in DOM-induced stimulus control might be important in mediating the stimulus effects of DOM. Fisher 344 rats were treated with either clozapine (25 mg/kg/day) or DOM (2 mg/kg/day) for 7 days, and the consequences of these drug treatment regimens on DOM-induced stimulus control and on 5-HT 2A receptor expression in several brain areas were determined. Chronic administration of clozapine was associated with a wide-spread decrease in levels of 5-HT 2A/2C receptors. Conversely, treatment with DOM had varied effects including a neuroanatomically selective decrease in 5-HT 2A/2C receptors levels that was restricted to the olfactory nucleus. Both chronic treatment with DOM and clozapine decreased the stimulus effects of DOM. The present findings suggest a role for the olfactory nucleus in producing the stimulus effects of DOM.

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Selective visualization of rat brain 5-HT2A receptors by autoradiography with [3H]MDL 100,907

Cited by 181 publications

References 31 publications

Dissociable Effects of Selective 5-HT2A and 5-HT2C Receptor Antagonists on Serial Spatial Reversal Learning in Rats

Dissociable Effects of Selective 5-HT2A and 5-HT2C Receptor Antagonists on Serial Spatial Reversal Learning in Rats

Role of 5-HT2A and 5-HT2B/2C Receptors in the Behavioral Interactions Between Serotonin and Catecholamine Reuptake Inhibitors

Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas

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