Tolerance to hypoactivity and sensitization to hyperactivity after chronic treatment with a presynaptic dose of lisuride in rats

Enzo Nisoli, Cristina Tonello, Maurizio Memo, Marina Pizzi, PierFranco Spano, Giuseppe Reina, Michele O. Carruba

Research output: Contribution to journalArticle

Abstract

We studied the adaptive changes of the locomotor effects of lisuride, a selective agonist for dopamine (DA) D2 receptors, and the functional state of D1 and D2 receptors after repeated administration of lisuride at a dose supposed to act preferentially on DA autoreceptors. Rats were treated daily with saline or lisuride, at a dose that causes a significant reduction in locomotor activity when given to naive rats (25 μg/kg i.p.), for 33 days and the effect of different challenging doses of the drug on locomotor activity was measured at different times during and after the treatment. The functional state of D1 and D2 DA receptors was evaluated by measuring SKF 82526-stimulated and LY 171555-inhibited adenylate cyclase (AC) activity in the caudatus/putamen, nucleus accumbens and substantia nigra and naive and chronically treated rats. There was a progressive decline in the ability of lisuride to decrease locomotor activity in rats given daily injections of lisuride, and there was a marked reduction in the threshold dose of lisuride for causing hypermotility. The functional state of DA receptors, positively or negatively linked to AC activity, was not modified by the treatment. The most suitable explanation of the reported adaptive behavioral changes is a down-regulation of DA autoreceptors after chronic treatment with presynaptic doses of lisuride.

Original languageEnglish
Pages (from-to)81-86
Number of pages6
JournalEuropean Journal of Pharmacology
Volume216
Issue number1
DOIs
Publication statusPublished - May 27 1992

Keywords

  • Adenylate cyclase activity
  • Dopamine autoreceptors
  • Lisuride
  • Locomotor activity
  • Sensitization
  • Tolerance

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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