Phencyclidine-induced abnormal behaviors in rats as measured by the hole board apparatus.
BACKGROUND
Phencyclidine (PCP) and methamphetamine (MAP) are known as psychotomimetic agents. Both agents produce behavioral alterations in animals.


OBJECTIVE
The present study investigated the difference in behavioral alterations in rats induced by these two psychotomimetic agents using the hole board apparatus (HBA). In addition, mechanisms underlying PCP-induced behavioral changes were also investigated.


METHODS
After the administration of PCP (1-4 mg/kg SC) or MAP (1-4 mg/kg SC), locomotor activity and dipping behavior were assessed using HBA. Effect of selective NMDA antagonists, (+)MK801 and 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), on rat behaviors were also assessed. The effects of D-alanine (D-Ala), a coagonist of NMDA receptors, or neuroleptics, haloperidol, clozapine and risperidone, on PCP-induced behavioral changes were investigated.


RESULTS
PCP increased locomotor activity and decreased exploratory behaviors of rats in HBA. On the other hand, MAP increased locomotor activity but did not decrease exploratory behaviors. (+)MK-801 produced hyperactivity as well as decreased exploratory behaviors, eliciting behavioral changes very similar to those of PCP. CPP decreased the exploratory behavior but failed to produce hyperactivity. D-Ala attenuated both behavioral changes induced by PCP. Three neuroleptics tested here inhibited hyperactivity but did not attenuate decreases in exploratory behavior.


CONCLUSIONS
These results suggest that PCP-induced decrease in exploratory behavior are attributable to antagonism of NMDA receptors and may not involve dopaminergic transmission via D2 receptors.
Morita
T
T
Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd, Tsukuba, Ibaraki, Japan. moritat@yamanouchi.co.jp
Sonoda
R
R
Nakato
K
K
Koshiya
K
K
Wanibuchi
F
F
Yamaguchi
T
T
D000409:Alanine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D010879:Piperazines; D008694:Methamphetamine; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D003024:Clozapine; D000409:Alanine; C015068:1-(3-chlorophenyl)piperazine