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The Effect of Subchronic Dosing of Ciproxifan and Clobenpropit on Dopamine and Histamine Levels in Rats.

Mahmood D, Pillai KK, Khanam R, Jahan K, Goswami D, Akhtar M - J Exp Neurosci (2015)

Bottom Line: MK-801-induced increase of horizontal activity was reduced with CPX and CBP.Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP.In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi, India.

ABSTRACT
The present study was designed to investigate the effect of once daily for 7-day (subchronic treatment) dosing of histamine H3 receptor antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p), including clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively, on MK-801(0.2 mg/kg, i.p.)-induced locomotor activity, and dopamine and histamine levels in rats. Dopamine and histamine levels were measured in striatum and hypothalamus, respectively, of rat brain. Atypical and typical antipsychotics were used to serve as clinically relevant reference agents to compare the effects of the H3 receptor antagonists. MK-801-induced increase of horizontal activity was reduced with CPX and CBP. The attenuation of MK-801-induced locomotor hyperactivity produced by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised dopamine levels in the striatum, which was reduced in rats pretreated with CPX and CBP. CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increase in histamine levels in the hypothalamus compared to the MK-801 treatment alone. Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP. In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

No MeSH data available.


The effect of subchronic dosing of histamine H3 receptor-ligands on MK 801-induced locomotor hyperactivity in rats.Note: MK-801 was given 10 minutes and RAMH 15 minutes before locomotor testing.Abbreviations: CPX, ciproxifan; CBP, clobenpropit; CPZ, chlorpromazine; CLZ, clozapine; MK-801, dizocilpine; NS, normal saline; RAMH, R-α-methylhistamine.
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f1-jen-9-2015-073: The effect of subchronic dosing of histamine H3 receptor-ligands on MK 801-induced locomotor hyperactivity in rats.Note: MK-801 was given 10 minutes and RAMH 15 minutes before locomotor testing.Abbreviations: CPX, ciproxifan; CBP, clobenpropit; CPZ, chlorpromazine; CLZ, clozapine; MK-801, dizocilpine; NS, normal saline; RAMH, R-α-methylhistamine.

Mentions: Rats treated subchronically with CPX or CBP exhibited a significant reduction of hyperlocomotor activities induced by a single-dose administration of MK-801 (0.2 mg/kg, i.p.). The horizontal activity increased from 2086.5 ±249.69 cm to 10577.10 ±249.69 cm[(P<0.01) F= 131.91(11,60)] following MK-801 administration. Rats treated subchronically with CPX or CBP showed a significant (CPX: P<0.01; CBP: P<0.01) reduction in hyperlocomotor activity induced by MK-801 (3103.18 ±255.02 cm and 3260.03 ±147.96 cm, respectively). The increased hyperlocomotor activity induced by MK-801 was also reduced (3342.72 ±213.30 cm and 4462.42 ±219.60 cm, respectively) significantly (CLZ: P<0.01; CPZ: P<0.01) following administration of CLZ (3.0 mg/kg, i.p.) or CPZ (3.0 mg/kg, i.p.). The protective effects of the administration of both the H3 antagonists were decreased (P<0.05) in RAMH (10 mg/kg, i.p.) pretreated groups. The MK-801-induced increase in horizontal activity was aggravated (P<0.05) following concurrent administration of RAMH and MK-801 (Fig. 1).


The Effect of Subchronic Dosing of Ciproxifan and Clobenpropit on Dopamine and Histamine Levels in Rats.

Mahmood D, Pillai KK, Khanam R, Jahan K, Goswami D, Akhtar M - J Exp Neurosci (2015)

The effect of subchronic dosing of histamine H3 receptor-ligands on MK 801-induced locomotor hyperactivity in rats.Note: MK-801 was given 10 minutes and RAMH 15 minutes before locomotor testing.Abbreviations: CPX, ciproxifan; CBP, clobenpropit; CPZ, chlorpromazine; CLZ, clozapine; MK-801, dizocilpine; NS, normal saline; RAMH, R-α-methylhistamine.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4556212&req=5

f1-jen-9-2015-073: The effect of subchronic dosing of histamine H3 receptor-ligands on MK 801-induced locomotor hyperactivity in rats.Note: MK-801 was given 10 minutes and RAMH 15 minutes before locomotor testing.Abbreviations: CPX, ciproxifan; CBP, clobenpropit; CPZ, chlorpromazine; CLZ, clozapine; MK-801, dizocilpine; NS, normal saline; RAMH, R-α-methylhistamine.
Mentions: Rats treated subchronically with CPX or CBP exhibited a significant reduction of hyperlocomotor activities induced by a single-dose administration of MK-801 (0.2 mg/kg, i.p.). The horizontal activity increased from 2086.5 ±249.69 cm to 10577.10 ±249.69 cm[(P<0.01) F= 131.91(11,60)] following MK-801 administration. Rats treated subchronically with CPX or CBP showed a significant (CPX: P<0.01; CBP: P<0.01) reduction in hyperlocomotor activity induced by MK-801 (3103.18 ±255.02 cm and 3260.03 ±147.96 cm, respectively). The increased hyperlocomotor activity induced by MK-801 was also reduced (3342.72 ±213.30 cm and 4462.42 ±219.60 cm, respectively) significantly (CLZ: P<0.01; CPZ: P<0.01) following administration of CLZ (3.0 mg/kg, i.p.) or CPZ (3.0 mg/kg, i.p.). The protective effects of the administration of both the H3 antagonists were decreased (P<0.05) in RAMH (10 mg/kg, i.p.) pretreated groups. The MK-801-induced increase in horizontal activity was aggravated (P<0.05) following concurrent administration of RAMH and MK-801 (Fig. 1).

Bottom Line: MK-801-induced increase of horizontal activity was reduced with CPX and CBP.Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP.In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi, India.

ABSTRACT
The present study was designed to investigate the effect of once daily for 7-day (subchronic treatment) dosing of histamine H3 receptor antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p), including clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively, on MK-801(0.2 mg/kg, i.p.)-induced locomotor activity, and dopamine and histamine levels in rats. Dopamine and histamine levels were measured in striatum and hypothalamus, respectively, of rat brain. Atypical and typical antipsychotics were used to serve as clinically relevant reference agents to compare the effects of the H3 receptor antagonists. MK-801-induced increase of horizontal activity was reduced with CPX and CBP. The attenuation of MK-801-induced locomotor hyperactivity produced by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised dopamine levels in the striatum, which was reduced in rats pretreated with CPX and CBP. CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increase in histamine levels in the hypothalamus compared to the MK-801 treatment alone. Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP. In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

No MeSH data available.