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Batool F, Haleem MA, Haleem DJ. Acute administration of clozapine and risperidone altered dopamine metabolism more in rat caudate than in nucleus accumbens: a dose-response relationship. Sci Pharm. 2009;78(2):259-74doi: 10.3797/scipharm.0907-20.
Batool, F., Haleem, M. A., & Haleem, D. J. (2010). Acute administration of clozapine and risperidone altered dopamine metabolism more in rat caudate than in nucleus accumbens: a dose-response relationship. Scientia pharmaceutica, 78(2), 259-74. https://doi.org/10.3797/scipharm.0907-20
Batool, Farhat, et al. "Acute administration of clozapine and risperidone altered dopamine metabolism more in rat caudate than in nucleus accumbens: a dose-response relationship." Scientia pharmaceutica vol. 78,2 (2010): 259-74. doi: https://doi.org/10.3797/scipharm.0907-20
Batool F, Haleem MA, Haleem DJ. Acute administration of clozapine and risperidone altered dopamine metabolism more in rat caudate than in nucleus accumbens: a dose-response relationship. Sci Pharm. 2010 Apr-Jun;78(2):259-74. doi: 10.3797/scipharm.0907-20. Epub 2009 Nov 29. PMID: 21179339; PMCID: PMC3002801.
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Sci Pharm. 2010 Apr-Jun;78(2):259-74. doi: 10.3797/scipharm.0907-20. Epub 2009 Nov 29.

Acute administration of clozapine and risperidone altered dopamine metabolism more in rat caudate than in nucleus accumbens: a dose-response relationship.

Scientia pharmaceutica

Farhat Batool, Muhammad A Haleem, Darakhshan J Haleem

Affiliations

  1. Neurochemistry and Biochemical Neuropharmacology Research Laboratory, Dept of Biochemistry, University of Karachi, Karachi-75270, Pakistan. [email protected]

PMID: 21179339 PMCID: PMC3002801 DOI: 10.3797/scipharm.0907-20

Abstract

The present study compares the extrapyramidal and neurochemical effects of clozapine and risperidone in rat caudate (corpus striatum) and nucleus accumbens (ventral striatum) dose-dependently. Animals injected with clozapine (2.5, 5.0 and 10.0 mg/kg IP) or risperidone (1.0, 2.5 and 5.0 mg/kg IP) in acute were sacrificed 1 h later to collect brain samples. Extrapyramidal side effects (EPS) in terms of locomotor activity and catalepsy were monitored in each animal after the drug or vehicle administration. Maximum cataleptic potentials were found only at high doses of clozapine (10.0 mg/kg; 60%) and risperidone (5.0 mg/kg; 100%). Neurochemical estimations were carried out by HPLC-EC. Both drugs at all doses significantly (p<0.01) increased the concentration of homovanillic acid (HVA), a metabolite of DA, in the caudate nucleus and decreased in nucleus accumbens. Levels of Dihydroxyphenylacetic acid (DOPAC) significantly (p<0.01) increased in the caudate by clozapine administration and decreased in the nucleus accumbens by the administration of both drugs in a dose-dependent manner. 5-Hydroxyindoleacetic acid (5-HIAA), the predominant metabolite of serotonin significantly decreased in the caudate and nucleus accumbens in a similar fashion. Levels of tryptophan (TRP) were remained insignificant in caudate and nucleus accumbens by the injections of two drugs. In caudate, clozapine and risperidone administrations significantly (p<0.01) decreased HVA/DA ratio and increased DOPAC/DA ratio in nucleus accumbens at all doses. The findings suggest the evidence for DA/5-HT receptor interaction as an important link in the lower incidence of EPS. The possible role of serotonin(1A) receptors in the pathophysiology of schizophrenia is also discussed.

Keywords: Atypical antipsychotics; Dopamine D2 receptors; Extrapyramidal side effects; Schizophrenia; Serotonin1A receptors

References

  1. Schizophr Res. 2008 Oct;105(1-3):224-35 - PubMed
  2. Prog Brain Res. 2008;172:199-212 - PubMed
  3. Am J Psychiatry. 2001 Mar;158(3):360-9 - PubMed
  4. Neuropsychopharmacology. 2002 Aug;27(2):143-51 - PubMed
  5. Neuropharmacology. 1996 Jan;35(1):119-21 - PubMed
  6. Br J Psychiatry. 1994 Feb;164(2):141-8 - PubMed
  7. Prog Brain Res. 2008;172:117-40 - PubMed
  8. Biol Psychiatry. 2001 Nov 15;50(10):729-42 - PubMed
  9. Med Sci Monit. 2002 Sep;8(9):BR354-61 - PubMed
  10. Drugs. 2008;68(16):2269-92 - PubMed
  11. Eur J Pharmacol. 1997 Apr 11;324(1):49-56 - PubMed
  12. Psychopharmacology (Berl). 1998 Apr;136(4):367-73 - PubMed
  13. J Clin Psychopharmacol. 2003 Feb;23(1):5-14 - PubMed
  14. Eur Neuropsychopharmacol. 2007 May-Jun;17(6-7):448-55 - PubMed
  15. Br J Psychiatry. 1999 Sep;175:231-8 - PubMed
  16. Lancet. 2009 Jan 3;373(9657):31-41 - PubMed
  17. Psychopharmacology (Berl). 2000 Jul;150(4):422-9 - PubMed
  18. Behav Pharmacol. 2008 Sep;19(5-6):548-61 - PubMed
  19. Pharmacol Rep. 2007 Mar-Apr;59(2):173-80 - PubMed
  20. J Pharmacol Exp Ther. 1989 Oct;251(1):238-46 - PubMed
  21. Arch Gen Psychiatry. 1990 Mar;47(3):213-9 - PubMed
  22. Int Clin Psychopharmacol. 1995 Mar;10(1):19-30 - PubMed
  23. Neuropsychopharmacology. 1997 Jul;17(1):44-55 - PubMed
  24. Psychopharmacology (Berl). 1996 Mar;124(1-2):74-86 - PubMed
  25. J Coll Physicians Surg Pak. 2009 Mar;19(3):139-45 - PubMed
  26. Prog Brain Res. 2008;172:177-97 - PubMed
  27. Life Sci. 1990;47(18):1609-15 - PubMed
  28. Psychopharmacology (Berl). 1989;99 Suppl:S28-31 - PubMed
  29. Br J Psychiatry. 2001 Dec;179:503-8 - PubMed
  30. CNS Drugs. 2009 Oct;23(10):837-55 - PubMed
  31. Eur J Pharmacol. 1980 May 2;63(2-3):135-44 - PubMed
  32. Pharmacol Biochem Behav. 2007 May;87(1):115-21 - PubMed
  33. Psychopharmacology (Berl). 1993;110(3):265-72 - PubMed
  34. Psychopharmacology (Berl). 1993;112(1 Suppl):S85-9 - PubMed
  35. Br J Psychiatry. 1994 Jan;164(1):16-26 - PubMed

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