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Psychopharmacology

, Volume 59, Issue 3, pp 211–216 | Cite as

Dopamine-receptor binding and adenylate-cyclase activity in mouse striatal tissue in the supersensitivity phase after neuroleptic treatment

  • John Hyttel
Original Investigations

Abstract

The specific binding of 3H-labelled haloperidol (3H-Hal) and the basal and dopamine-stimulated adenylate-cyclase activity in vitro were investigated in mice treated with a single dose or with repeated doses of neuroleptic drugs. These dose regimens are known to induce behavioural supersensitivity and to decrease dopamine synthesis and release a few days after cessation of dosage.

Shortly after a single dose of teflutixol (5 mg/kg i.p.) the binding of 3H-Hal was reduced to very low levels. Four and five days later the apparent number of receptor-binding sites was slightly reduced. The binding returned to normal levels after 6 days. The reduced binding most likely reflects the receptor blockade induced by teflutixol. Four days after treatment both basal and dopamine-stimulated adenylate cyclase were within normal limits. Six days following a single dose of piflutixol (0.08 mg/kg i.p.) a light increase in dopamine-stimulated adenylate cyclase activity was observed. Three days after repeated doses of haloperidol (1.25 mg/kg p.o. daily for 5 days), both basal and dopamine-stimulated adenylate cyclase were unchanged. After 3 weeks treatment with teflutixol (5 mg/kg i.p. daily), the specific binding of 3H-Hal was slightly reduced 5 days after, but almost equal to controls 8 days after the last dose.

The data presented neither support nor reject the hypothesis of an increased number of DA receptors in the supersensitivity phase after neuroleptic treatment of mice.

Key words

3H-Haloperidol binding Adenylate cyclase c-AMP Supersensitivity Neuroleptics 

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Copyright information

© Springer-Verlag 1978

Authors and Affiliations

  • John Hyttel
    • 1
  1. 1.Department of Pharmacology and ToxicologyH. Lundbeck & Co. A/SValbyDenmark

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