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Effects of pertussis toxin on behavioral responses during different withdrawal periods from chronic cocaine treatment.

Abstract：

:1. The role of Gi-proteins on cataleptic responses induced by SCH23390 and haloperidol in chronic cocaine-treated mice was examined by intracerebroventricullor (i.c. v.) and intravenous (i. v.) injections of pertussis toxin (PTX), which catalyzes adenosine diphosphate (ADP)-ribosylation of Gi-proteins. 2. In animals pretreated chronically with cocaine (10 mg/kg, s.c. on alternating days for 21 days), haloperidol (0.1 mg/kg i.p.) exerted an enhanced cataleptic response, but SCH23390 (0.1 mg/kg i.p.) produced an attenuated response at day 1, which converted to a supernormal response, when it was administered 20 days after the last cocaine injection. 3. The attenuated SCH23390 cataleptic response (D1 receptor supersensitivity induced one day after chronic cocaine treatment), was reversed one day after a single dose of PTX, which by itself had no effect, whereas the enhanced haloperidol catalepsy was further enhanced with same dose of toxin. 4. On the other hand, the enhanced SCH23390- and haloperidol-induced cataleptic responses seen during longer withdrawal period (20 days) were potentiated 20 days after a single coadministration of PTX. The stimulatory effects of PTX on the enhanced SCH23390-induced cataleptic response (D1 receptor subsensitivity induced during long-term withdrawal periods from chronic cocaine treatment), may be due to an indirect inhibition of D1 receptors (a synergistic effect) via blockade of postsynaptic dopamine D2 receptors. 5. The postsynaptic D1 receptor supersensitivity and D2 receptor subsensitivity induced one day after chronic cocaine treatment may involve greater Gi-protein ADP-ribosylation in the presynaptic cell body (VTA) than that in the postsynaptic cell body. On the other hand, the subsensitivity of postsynaptic dopamine D1 and D2 receptors (the enhanced SCH23390- and haloperidol-induced cataleptic responses) seen during longer withdrawal periods may mainly involve Gi-protein ADP ribosylation in the postsynaptic cell body, and which may be mediated by a PTX-sensitive muscarinic M2 and/orGABAB receptor activation.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Ushijima I,Mizuki Y,Kobayashi T,Aoki T,Suetsugi M,Usami K,Watanabe Y

doi

10.1016/s0278-5846(00)00134-2

subject

Has Abstract

pub_date

2000-11-01 00:00:00

pages

1369-77

issue

8

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(00)00134-2

journal_volume

24

pub_type

杂志文章

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