Effects of the H(3) antagonist, thioperamide, on behavioral alterations induced by systemic MK-801 administration in rats.
BACKGROUND
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.


OBJECTIVE
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.
Bardgett
Mark E
ME
Department of Psychology, Northern Kentucky University, Highland Heights, KY 41076, USA. bardgettm@nku.edu
Points
Megan
M
Roflow
John
J
Blankenship
Meredith
M
Griffith
Molly S
MS
D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D054828:Histamine H3 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D008297:Male; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D013216:Reflex, Startle / Q000187:drug effects*; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy
D054828:Histamine H3 Antagonists; D010880:Piperidines; D016291:Dizocilpine Maleate; C052075:thioperamide