RATIONALE: Recent studies have raised the possibility that antagonists of H(3) histamine receptors possess cognitive-enhancing and antipsychotic properties. However, little work has assessed these compounds in classic animal models of schizophrenia. OBJECTIVES: The purpose of this study was to determine if a prototypical H(3) antagonist, thioperamide, could alter behavioral deficits caused by the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801, in adult male rats. MK-801 was chosen to be studied since it produces a state of NMDA receptor hypofunction in rats that may be analogous to the one hypothesized to occur in schizophrenia. METHODS: The interaction between thioperamide and MK-801 was measured in three behavioral tests: locomotor activity, prepulse inhibition (PPI), and delayed spatial alternation. In each test, rats received a subcutaneous injection of saline or thioperamide (3.0 and 10 mg/kg) followed 20 min later by a subcutaneous injection of saline or MK-801 (0.05, 0.10, and 0.30 mg/kg). RESULTS: Locomotor activity was significantly elevated by MK-801 in a dose-dependent manner. Thioperamide pretreatment alone did not alter locomotor activity; however, its impact on MK-801 was dose-dependent. Each thioperamide dose enhanced the effects of two lower doses of MK-801 but reduced the effect of a higher MK-801 dose. Clear deficits in PPI and delayed spatial alternation were produced by MK-801 treatment, but neither impairment was significantly modified by thioperamide pretreatment. CONCLUSIONS: H(3) receptors modulate responses to NMDA antagonists in behaviorally specific and dose-dependent ways.
RATIONALE: Recent studies have raised the possibility that antagonists of H(3)histamine receptors possess cognitive-enhancing and antipsychotic properties. However, little work has assessed these compounds in classic animal models of schizophrenia. OBJECTIVES: The purpose of this study was to determine if a prototypical H(3) antagonist, thioperamide, could alter behavioral deficits caused by the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801, in adult male rats. MK-801 was chosen to be studied since it produces a state of NMDA receptor hypofunction in rats that may be analogous to the one hypothesized to occur in schizophrenia. METHODS: The interaction between thioperamide and MK-801 was measured in three behavioral tests: locomotor activity, prepulse inhibition (PPI), and delayed spatial alternation. In each test, rats received a subcutaneous injection of saline or thioperamide (3.0 and 10 mg/kg) followed 20 min later by a subcutaneous injection of saline or MK-801 (0.05, 0.10, and 0.30 mg/kg). RESULTS: Locomotor activity was significantly elevated by MK-801 in a dose-dependent manner. Thioperamide pretreatment alone did not alter locomotor activity; however, its impact on MK-801 was dose-dependent. Each thioperamide dose enhanced the effects of two lower doses of MK-801 but reduced the effect of a higher MK-801 dose. Clear deficits in PPI and delayed spatial alternation were produced by MK-801 treatment, but neither impairment was significantly modified by thioperamide pretreatment. CONCLUSIONS:H(3) receptors modulate responses to NMDA antagonists in behaviorally specific and dose-dependent ways.
Authors: Gerard B Fox; Jia Bao Pan; Richard J Radek; Angela M Lewis; R Scott Bitner; Timothy A Esbenshade; Ramin Faghih; Youssef L Bennani; Michael Williams; Betty B Yao; Michael W Decker; Arthur A Hancock Journal: J Pharmacol Exp Ther Date: 2003-02-20 Impact factor: 4.030
Authors: J C Schwartz; S Morisset; A Rouleau; X Ligneau; F Gbahou; J Tardivel-Lacombe; H Stark; W Schunack; C R Ganellin; J M Arrang Journal: J Neural Transm Suppl Date: 2003
Authors: S Morisset; C Pilon; J Tardivel-Lacombe; D Weinstein; W Rostene; C Betancur; P Sokoloff; J C Schwartz; J M Arrang Journal: J Pharmacol Exp Ther Date: 2002-02 Impact factor: 4.030
Authors: Kaitlin E Browman; Victoria A Komater; Peter Curzon; Lynne E Rueter; Arthur A Hancock; Michael W Decker; Gerard B Fox Journal: Behav Brain Res Date: 2004-08-12 Impact factor: 3.332
Authors: Andrea M Bradford; Kevin M Savage; Declan N C Jones; Mikhail Kalinichev Journal: Psychopharmacology (Berl) Date: 2010-07-31 Impact factor: 4.530
Authors: Mark E Bardgett; Megan Points; Jennifer Kleier; Meredith Blankenship; Molly S Griffith Journal: Neuropharmacology Date: 2010-07-16 Impact factor: 5.250