Effect of MS-153 on the development of behavioral sensitization to locomotion- and ataxia-inducing effects of phencyclidine.
BACKGROUND
Repeated administration of phencyclidine (PCP) produces behavioral sensitization to PCP. Although the precise mechanism is unknown, glutamatergic neurotransmission seems to play an important role in the development of sensitization.


OBJECTIVE
The present study examined whether a novel compound, MS-153 (( R)-(-)-5-methyl-1-nicotinyl-2-pyrazoline), which has an ability to enhance glutamate uptake and inhibit glutamate release, would block the development of behavioral sensitization to PCP.


METHODS
For studying effects of MS-153, locomotor activity was measured by an infrared sensor and ataxia was measured by a rating scale.


RESULTS
MS-153 (10 and 100 mg/kg) enhanced locomotion and ataxia induced by a single injection of PCP (7.5 mg/kg). Repeated administration of PCP (20 mg/kg, once in every day, for 5 days) developed sensitization to locomotion- and ataxia-inducing effects of PCP (7.5 mg/kg). MS-153 given 60 min and 120 min later of every PCP treatment blocked the development of behavioral sensitization to both locomotion- and ataxia-inducing effects of PCP. Co-administration of MS-153 with repeated saline treatment did not produce hypersensitivity to PCP.


CONCLUSIONS
These results suggest that the attenuation of glutamatergic neural transmission enhances acute effects of PCP, in contrast, blocks the behavioral sensitization developed by repeated PCP treatment. Therefore, glutamatergic neural transmission plays an important role in the development of behavioral sensitization to PCP.
Abekawa
T
T
Department of Psychiatry, Hokkaido University, Graduate School of Medicine, Kita 15, Nishi 7, Sapporo 060-8638, Japan.
Honda
M
M
Ito
K
K
Inoue
T
T
Koyama
T
T
D000818:Animals; D001259:Ataxia / Q000139:chemically induced* / Q000188:drug therapy*; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects*; D007274:Injections, Intraperitoneal; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009539:Nicotinic Acids / Q000494:pharmacology*; D010622:Phencyclidine / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019956:Stereotypic Movement Disorder / Q000139:chemically induced / Q000188:drug therapy; D013997:Time Factors
C101692:5-methyl-1-nicotinoyl-2-pyrazoline; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D009539:Nicotinic Acids; D010622:Phencyclidine