The D-1 dopamine receptor antagonist SCH 23390 also interacts potently with brain serotonin (5-HT2) receptors

Bischoff, Serge; Heinrich, Micheline; Sonntag, Jean Marie; Krauss, J.

doi:10.1016/0014-2999(86)90449-8

Cited by 240 publications

(82 citation statements)

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“…Raclopride is selective for dopamine D2 and D3 subtypes, and has no other known receptor interactions ). In addition, although high doses of SCH23390 have been reported to protect 5HT 2C receptors (Meller et al 1985), the low doses used in the present study selectively protect D1 receptors, because of the 10-fold higher affinity of SCH23390 for D1 compared with 5HT 2C receptors in vivo (Bischoff et al 1986). Finally, our past studies have demonstrated that antagonism of serotonin receptors does not result in increases in EMG activity (Crocker 1995).…”

Section: Discussionmentioning

confidence: 68%

Changes in Muscle Tone Are Regulated by D1 and D2 Dopamine Receptors in the Ventral Striatum and D1 Receptors in the Substantia Nigra

Hemsley

Crocker

2001

Neuropsychopharmacology

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Muscle rigidity associated with antipsychotic drug treatment is believed to result from reduced striatal dopamine neurotransmission. In the current study the regulatory roles of dopamine D1 and D2 receptor subfamilies in the dorsal (DSTR) and ventral striatum (VSTR) and substantia nigra (SN) were investigated on muscle tone, assessed as increases in tonic electromyographic (EMG) activity. Rats were injected with the irreversible The use of antipsychotic drugs to treat the symptoms of schizophrenia can be associated with extrapyramidal side effects, which resemble the symptoms of Parkinson's disease and include increased muscle rigidity in up to 40% of patients (Baldessarini and Tarsy 1980). Further, it has been estimated that up to 30% of patients stop taking their medication because of these motor side effects (Hoge et al. 1990). It is not fully understood why antipsychotic drugs, all antagonists at the dopamine D2 receptor (Creese et al. 1976;Seeman et al. 1976; Peroutka and Snyder 1980) produce motor side effects, although there is some early experimental evidence supporting the view that antagonism of D2 receptors in the striatum is important (Chiodo and Bunney 1983;Creese 1983). Findings from studies in humans using positron emission tomography (PET) have led to the concept that a "threshold" of D2 antagonism by antipsychotic drugs of approximately 70%, exists in the striatum, above which patients experience motor side effects (Farde et al. 1992;Nordstrom et al. 1995). Additional support for the striatal D2 threshold hypothesis has N EUROPSYCHOPHARMACOLOGY 2001 -VOL . 25 , NO . 4 Dopamine D1 & D2 Receptors Regulate Muscle Tone 515 been provided by studies using experimental animals Ogren et al. 1994;Alcock and Crocker 1999;Hemsley and Crocker 1999a) and other imaging techniques in humans (Scherer et al. 1994). Further, it has been reported that clozapine, which does not produce motor side effects in humans or animals (Claghorn et al. 1987;Casey 1989), occupies sub-threshold levels of D2 receptors in the striatum (Farde et al. 1992;Hemsley and Crocker 1999a) and substantia nigra (Hemsley and Crocker 1999a). The role of dopamine D1 receptors in the production of motor side effects is unclear, and no relationship to D1 receptor occupancy was shown in PET studies (Farde et al. 1992). However, there is evidence that antagonism of D1 receptors may result in motor side effects Sedvall et al. 1995) and elicit such motor behaviors as catalepsy in rats (Ogren and Fuxe 1988). As many commonly used antipsychotic drugs, such as chlorpromazine, fluphenazine, and clozapine, are also potent dopamine D1 antagonists (Hacksell et al. 1995), it would be useful to understand the contribution that antagonism of the D1 receptor subfamily makes to the production of muscle rigidity.Experimental research investigating the mechanisms underlying the motor side effects associated with the use of antipsychotic drugs has been handicapped by the lack of a relevant, objective, and quantifiable endpoint of extrapyramidal side effects ...

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Section: Discussionmentioning

confidence: 68%

Changes in Muscle Tone Are Regulated by D1 and D2 Dopamine Receptors in the Ventral Striatum and D1 Receptors in the Substantia Nigra

Hemsley

Crocker

2001

Neuropsychopharmacology

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“…It should be noted that SCH 23390 binds with high affinity to 5-HT 2A receptors (Bischoff et al, 1986). However, the doses used in the present experiment are thought to be selective for the D 1 class and to avoid the interactions with 5-HT 2A receptors found at higher doses (Bischoff et al, 1986;Hess et al, 1986). Experiment 2 tested the effects of the D 2 antagonist haloperidol (0.005, 0.01, and 0.05 mg/kg).…”

Section: Introductionmentioning

confidence: 81%

Selective Alleviation of Compulsive Lever-Pressing in Rats by D1, but not D2, Blockade: Possible Implications for the Involvement of D1 Receptors in Obsessive–Compulsive Disorder

Joel

Doljansky

2003

Neuropsychopharmacol

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Rats undergoing extinction of lever-pressing for food after the attenuation of an external feedback for this behavior exhibit excessive lever-pressing unaccompanied by an attempt to collect a reward. This behavior may be analogous to the excessive and unreasonable behavior seen in obsessive-compulsive disorder. In the present study, we tested the hypothesis that the compulsive behavior induced by signal attenuation is mediated via D 1 rather than D 2 receptors. Administration of 0.005, 0.01 and 0.03 mg/kg of the D 1 antagonist SCH 23390 reduced the number of compulsive lever-presses without affecting the number of lever-presses followed by an attempt to collect a reward. In contrast, administration of 0.005, 0.01, 0.024, 0.036 and 0.05 of the D 2 antagonist haloperidol dose-dependently decreased both types of lever-presses. In addition, haloperidol at doses that decreased lever-pressing in the post-training signal attenuation procedure (0.036 and 0.05 mg/kg) had a similar effect in regular extinction, whereas an SCH 23390 dose that decreased compulsive lever-pressing in the post-training signal attenuation procedure (0.01 mg/kg) had no effect on regular extinction. On the basis of electrophysiological data on the response of dopamine neurons to the omission of an expected reward, these results were interpreted as suggesting that compulsive lever-pressing depends on a phasic decrease in the stimulation of D 1 receptors. The implications of these results for the pathophysiology and treatment of obsessive-compulsive disorder are discussed.

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“…It should be mentioned that SCH 23390 acts not only as a D1 receptor antagonist, but also as a 5-HT2 receptor competitive antagonist (Ohlstein and Berkowitz, 1985;Bischoff et al, 1986). To our knowledge, there have been no published studies on the role of 5-HT2 receptor in the PFC, in spatial learning in rodents.…”

Section: Prefrontal Cortex Dopamine In Spatial Learningmentioning

confidence: 99%

D1 and D2 Receptor Antagonist Injections in the Prefrontal Cortex Selectively Impair Spatial Learning in Mice

Rinaldi

Mandillo

Oliverio

et al. 2006

Neuropsychopharmacol

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The prefrontal cortex (PFC) is a cortical area involved in selecting and retaining information to produce complex behaviors. Within the PFC, the dopaminergic system plays an important role in information processing. Thus, the objective of this study was to test whether bilateral administration of the D1 and D2 receptor antagonists in the prelimbic region of the PFC influenced the performance of mice in a non-associative spatial learning task. CD1 mice were bilaterally microinjected in the PFC with either the D1 receptor antagonist, SCH23390 (SCH 6.25; 12.5; 50 ng), or the D2 receptor antagonist, sulpiride (SULP 12.5; 50; 100 ng) and placed into an open field containing five different objects. After three sessions of habituation two objects were repositioned (spatial change) and in the subsequent session one of the objects was substituted (non-spatial change). No significant alteration was observed in the habituation pattern of the animals after D1 or D2 receptor blockade. When two of the objects were displaced, control mice explored the displaced objects far more than the non-displaced ones, while mice treated with SCH or SULP spent a comparable amount of time re-exploring the two object categories. Conversely, DA antagonists had no effects on the discrimination of the new object. Thus, the administration of both SCH and SULP selectively impaired the ability of mice to discriminate a spatial change, without affecting any other behavioral parameter. These findings could provide a model to study the role of the PFC dopaminergic system in spatial learning and to study the neural mechanisms underlying cognitive and attention deficits often observed in psychiatric disorders.

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The D-1 dopamine receptor antagonist SCH 23390 also interacts potently with brain serotonin (5-HT2) receptors

Cited by 240 publications

References 6 publications

Changes in Muscle Tone Are Regulated by D1 and D2 Dopamine Receptors in the Ventral Striatum and D1 Receptors in the Substantia Nigra

Changes in Muscle Tone Are Regulated by D1 and D2 Dopamine Receptors in the Ventral Striatum and D1 Receptors in the Substantia Nigra

Selective Alleviation of Compulsive Lever-Pressing in Rats by D1, but not D2, Blockade: Possible Implications for the Involvement of D1 Receptors in Obsessive–Compulsive Disorder

D1 and D2 Receptor Antagonist Injections in the Prefrontal Cortex Selectively Impair Spatial Learning in Mice

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