Anticataleptic 8-OH-DPAT preferentially counteracts with haloperidol-induced Fos expression in the dorsolateral striatum and the core region of the nucleus accumbens

Ohno, Yukihiro; Shimizu, Saki; Imaki, Junta; Ishihara, Shizuka; Sofue, Nobumasa; Sasa, Masashi; Kawai, Yoshiko

doi:10.1016/j.neuropharm.2008.06.005

Cited by 40 publications

(32 citation statements)

References 28 publications

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“…1,[3][4][5] Several studies demonstrated that activation of 5-HT 1A receptors improves antipsychotic-induced EPS and motor disabilities in animal models of Parkinson's disease. [10][11][12][13][14][15][16] In our studies, 5-HT 1A agonists (e.g., 8-hydroxy-2-(di-n-propylamino)-tetralin and tandospirone) ameliorated haloperidol-induced bradykinesia and catalepsy with potencies similar to those of antiparkisonian agents (e.g., trihexyphenidyl and L-3,4-dihydroxyphenylalanine (L-DOPA)). 13,14) Consistently with these anti-EPS actions, 5-HT 1A agonists reversed striatal Fos protein expression induced by haloperidol, indicating that 5-HT 1A receptors counteract D 2 receptor blockade by antipsychotics in the striatum.…”

Section: Roles Of 5-ht Receptors In Modulating Extrapyramidal Motor Dmentioning

confidence: 57%

“…13,14) Consistently with these anti-EPS actions, 5-HT 1A agonists reversed striatal Fos protein expression induced by haloperidol, indicating that 5-HT 1A receptors counteract D 2 receptor blockade by antipsychotics in the striatum. 14,15) Earlier studies showed that microinjection of 5-HT 1A agonists into the raphe nuclei attenuated antipsychotic-induced catalepsy, suggesting that activation of presynaptic 5-HT 1A autoreceptors can reduce EPS 11) ( Fig. 1 and Table 1).…”

Section: Roles Of 5-ht Receptors In Modulating Extrapyramidal Motor Dmentioning

confidence: 69%

“…[10][11][12][13][14][15][16] In our studies, 5-HT 1A agonists (e.g., 8-hydroxy-2-(di-n-propylamino)-tetralin and tandospirone) ameliorated haloperidol-induced bradykinesia and catalepsy with potencies similar to those of antiparkisonian agents (e.g., trihexyphenidyl and L-3,4-dihydroxyphenylalanine (L-DOPA)). 13,14) Consistently with these anti-EPS actions, 5-HT 1A agonists reversed striatal Fos protein expression induced by haloperidol, indicating that 5-HT 1A receptors counteract D 2 receptor blockade by antipsychotics in the striatum. 14,15) Earlier studies showed that microinjection of 5-HT 1A agonists into the raphe nuclei attenuated antipsychotic-induced catalepsy, suggesting that activation of presynaptic 5-HT 1A autoreceptors can reduce EPS 11) ( Fig.…”

Section: Roles Of 5-ht Receptors In Modulating Extrapyramidal Motor Dmentioning

confidence: 74%

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Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

Ohno

Shimizu

Tokudome

2013

Biological & Pharmaceutical Bulletin

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The serotonergic nervous system plays crucial roles in regulating psycho-emotional, cognitive, sensorimotor and autonomic functions. It is now known that multiple serotonin (5-hydroxytryptamine; 5-HT) receptors regulate extrapyramidal motor functions, which are implicated in pathogenesis and/or treatment of various neurological disorders (e.g., Parkinson's disease and drug-induced extrapyramidal motor deficits).

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Section: Roles Of 5-ht Receptors In Modulating Extrapyramidal Motor Dmentioning

confidence: 57%

Section: Roles Of 5-ht Receptors In Modulating Extrapyramidal Motor Dmentioning

confidence: 69%

Section: Roles Of 5-ht Receptors In Modulating Extrapyramidal Motor Dmentioning

confidence: 74%

See 1 more Smart Citation

Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

Ohno

Shimizu

Tokudome

2013

Biological & Pharmaceutical Bulletin

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“…The catalepsy test was carried out as described previously (10). Briefly, the fore paws of the animals were placed on a horizontal bar positioned at 5 cm above the bench surface, and the time spent for the animals to show the cataleptic posture, which was defined as an immobile posture while keeping both forelimbs on the bar, was measured with a maximum limit of 30 s.…”

Section: Catalepsy Testmentioning

confidence: 99%

“…Consistent with previous findings (4,7,9), our results suggest that 8-OH-DPAT alleviates APD-induced EPS probably through activating postsynaptic 5-HT 1A receptors (including heteroreceptors). In addition, anticataleptic 8-OH-DPAT reversed the haloperidol (D 2 antagonism)-induced Fos expression in the dorsolateral striatum (dlST) and the core region of the nucleus accumbens (AcC), without affecting other brain regions examined (10). Thus, it was suggested that stimulation of 5-HT 1A receptors could reduce the D 2 -blocking actions of APDs specifically in brain regions (i.e., dlST and AcC) that are related to EPS induction (11 -13).…”

Section: Introductionmentioning

confidence: 99%

Effects of Tandospirone, a 5-HT1A Agonistic Anxiolytic Agent, on Haloperidol-Induced Catalepsy and Forebrain Fos Expression in Mice

2009

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Abstract. We studied the effects of tandospirone, a 5-HT 1A agonistic anxiolytic agent, on haloperidol-induced catalepsy and forebrain Fos expression in mice. Haloperidol (0.5 mg/kg, i.p.) markedly increased the catalepsy time and enhanced Fos expression in the shell (AcS) and core (AcC) regions of the nucleus accumbens, the dorsolateral striatum (dlST), and the lateral septal nucleus (LSN). Tandospirone (0.1 -1 mg/kg, s.c.) significantly alleviated haloperidolinduced catalepsy in a dose-dependent manner, which was antagonized by WAY-100135 (a selective 5-HT 1A antagonist). The anticataleptic dose of tandospirone (1 mg/kg, s.c.) significantly reduced haloperidol-induced Fos expression in the dlST. This inhibition by tandospirone was regionally specific, and it failed to affect haloperidol-induced Fos expression either in the AcS, AcC, or LSN. In addition, the reversal of haloperidol-induced striatal Fos expression by tandospirone was antagonized by WAY-100135. These results support the notion that stimulation of 5-HT 1A receptors region-specifically counteracts the D 2 -blocking actions of haloperidol in the striatum, which may account for the ameliorative effects of 5-HT 1A agonists on antipsychoticassociated extrapyramidal disorders.

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Fos expression in response to dopamine D3-preferring phenylpiperazine drugs given with and without cocaine

Nolan

Liu

Hammerslag

et al. 2013

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WC 44 and WC 10 are phenylpiperazines with low (23 fold) to moderate (42 fold) selectivity for dopamine D3 receptors (D3Rs) over D2Rs, respectively. WC 44 is a full D3R agonist in the forskolin-stimulated adenylyl cyclase (AC) assay, whereas WC 10 has little efficacy. In contrast to their opposite effects in the AC assay, these drugs often produce similar behavioral effects, suggesting that the AC assay does not predict the efficacy of these drugs in vivo. Here we examined whether Fos protein expression induced by these drugs would be more consistent with their behavioral effects in vivo. Rats received either vehicle, WC 10 (5.6 mg/kg, i.p.), WC 44 (10.0 mg/kg, i.p), cocaine (10.0 mg/kg, i.p.), or cocaine with WC 10 (5.6 mg/kg, i.p.) or with WC 44 (10.0 mg/kg, i.p). Locomotion was monitored for 90 min and the brains were harvested for immunohistochemistry. Both WC 10 and WC 44 decreased spontaneous and cocaine-induced locomotion. Both compounds also increased Fos expression relative to saline in the dorsal striatum and nucleus accumbens core and shell, and relative to cocaine alone in the nucleus accumbens shell. The findings suggest that even though these compounds have different efficacy in the AC bioassy, they produce similar brain activation and attenuation of cocaine hyperlocomotion. Together with our previous research demonstrating that these compounds down-shift the cocaine self-administration dose-effect function, the findings support the idea that D3R-selective compounds may be useful for cocaine dependence medications development.

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Anticataleptic 8-OH-DPAT preferentially counteracts with haloperidol-induced Fos expression in the dorsolateral striatum and the core region of the nucleus accumbens

Cited by 40 publications

References 28 publications

Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

Effects of Tandospirone, a 5-HT1A Agonistic Anxiolytic Agent, on Haloperidol-Induced Catalepsy and Forebrain Fos Expression in Mice

Fos expression in response to dopamine D3-preferring phenylpiperazine drugs given with and without cocaine

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