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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.CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP.Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP.

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 brain dopamine level in MK 801 treated rats.Note: MK-801 was given 10 minutes before 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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f3-jen-9-2015-073: The effect of subchronic dosing of histamine H3 receptor-ligands on brain dopamine level in MK 801 treated rats.Note: MK-801 was given 10 minutes before 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: The administration of MK-801 (0.2 mg/kg, i.p.) caused elevation (P<0.05) of the striatal dopamine level in comparison to vehicle-treated group. In CPX (3.0 mg/kg, i.p.) and CBP (15 mg/kg, i.p.) pretreated groups, there was a reduction (P<0.05; [F= 16.84(11,60]) in MK-801-induced increase in the striatal dopamine levels, which was recorded as 2580.31 ±219.80 ng/g-tissue and 2593.54 ±283.44 ng/g-tissue, respectively. The administration of CLZ or CPZ (3.0 mg/kg, i.p.) also reduced (P<0.05) the increased striatal dopamine level induced by MK-801. The reduction in striatal dopamine level mediated by CLZ or CPZ was comparable to the reduction produced by CPX or CBP administration. The decrease of striatal dopamine level mediated by the administration of CPX and CBP further tended to elevate (P<0.05) in RAMH (10 mg/kg, i.p.) pretreated group whencompared with CPX+MK-801 and CBP+MK-801 groups, respectively (Figs. 2 and 3).


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 brain dopamine level in MK 801 treated rats.Note: MK-801 was given 10 minutes before 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

Show All Figures
getmorefigures.php?uid=PMC4556212&req=5

f3-jen-9-2015-073: The effect of subchronic dosing of histamine H3 receptor-ligands on brain dopamine level in MK 801 treated rats.Note: MK-801 was given 10 minutes before 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: The administration of MK-801 (0.2 mg/kg, i.p.) caused elevation (P<0.05) of the striatal dopamine level in comparison to vehicle-treated group. In CPX (3.0 mg/kg, i.p.) and CBP (15 mg/kg, i.p.) pretreated groups, there was a reduction (P<0.05; [F= 16.84(11,60]) in MK-801-induced increase in the striatal dopamine levels, which was recorded as 2580.31 ±219.80 ng/g-tissue and 2593.54 ±283.44 ng/g-tissue, respectively. The administration of CLZ or CPZ (3.0 mg/kg, i.p.) also reduced (P<0.05) the increased striatal dopamine level induced by MK-801. The reduction in striatal dopamine level mediated by CLZ or CPZ was comparable to the reduction produced by CPX or CBP administration. The decrease of striatal dopamine level mediated by the administration of CPX and CBP further tended to elevate (P<0.05) in RAMH (10 mg/kg, i.p.) pretreated group whencompared with CPX+MK-801 and CBP+MK-801 groups, respectively (Figs. 2 and 3).

Bottom Line: MK-801-induced increase of horizontal activity was reduced with CPX and CBP.CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP.Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP.

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.