Correlation Between Behavioral Alteration to Chronic Cocaine Treatment and G-Protein ADP-Ribosylation in Mice.

Creators Ushijima Itsuko

Creators Kobayashi Takayoshi

Creators Akimoto Takashi

Creators Jing Sheng Zi

Creators Mitsuno Shigeru

Creators Watanabe Katsumi

Creators Yamada Michio

The role of Gi-proteins on cataleptic responses induced by SCH23390, a dopamine D1 receptor antagonist, and haloperidol, a mainly dopamine D2 receptor antagonist, one day after chronic cocaine treatment in mice was examined by injecting intravenously (i.v.) pertussis toxin, which catalyzes adenosine diphosphate (ADP)-ribosylation of Gi-proteins. SCH23390- and haloperidol-induced catalepsy was potentiated 3-24 h after administration of a single dose (5 and 10mg/kgi.v.) of the toxin, but not at 1 mg/kg. It was apparent that the longer the time interval between pertussis toxin and dopamine antagonists treatments, snd the higher the dose of pertussis toxin, the greater were the cataleptic reponses. Mice given subcutaneous administration (s.c.) of cocaine (10mg/kg) once every other day for 15 days (a total of 8 injections) exhibited an attenuated SCH23390-induced catalepsy (SCH23390 catalepsy) and an enhanced haloperidol-induced catalepsy (haloperidol catalepsy9 one day after the last cocaine injection.The inhibitory effect of chronic cocaine treatment on SCH23390 catalepsy was enhancing effect of that on haloperidol catalepsy was fuether enhanced with same dose of toxin. These results suggest that there may be an interrelationship between Gi-protein ADP-ribosylation and D2 receptor subsensivity (enhanced haloperidol catalepsy) induced by chronic cocaine treatment, whereas an opposite relationship exists between D1 peceptor supersensitivity (attenuation of SCH23390 catalepsy) induced by chronic cocain treatment and the ribosylation. Accordingly, behavioral sensitization (reverse tolerance) seen one day after chronic cocaine treatment, which result in D1 ewcwptor supersensitivity and D2 receptor subsensitivity may not involve Gi protein ADP-rebosylation.

[ISSN]0513-1812

[NCID]AA00594272