Lithium dissociates haloperidol-induced behavioral supersensitivity from reduced dopac increase in rat striatum

Emanuel Meller, Eitan Friedman

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic lithium administration prevents both haloperidol-induced dopaminergic behavioral supersensitivity and increased tritiated neuroleptic binding to dopamine (DA) receptors in rat corpus striatum. Since chronic haloperidol treatment also induces tolerance to the activating effects of the drug on striatal DA synthesis, the ability of lithium to block neurochemical tolerance development was investigated. Whereas lithium treatment significantly (P<0.01) attenuated haloperidol-induced behavioral supersensitivity to apomorphine (0.33 and 0.66 mg/kg s.c.), it did not prevent tolerance to the elevation of striatal 3,4-dihydroxyphenylacetic acid (DOPAC) levels 1 h after the last treatment or in response to challenge with a low dose (0.1 mg/kg) of haloperidol during withdrawal. These results demonstrate a dissociation between the development of behavioral supersensitivity and the reduction in DOPAC increase. An assessment of lithium's demonstrated effects on supersensitivity development at various DA receptor sites suggests that tolerance may be mediated by presynaptic DA receptors on terminals of nigrostriatal neurons.

Original languageEnglish
Pages (from-to)25-29
Number of pages5
JournalEuropean Journal of Pharmacology
Volume76
Issue number1
DOIs
StatePublished - 19 Nov 1981
Externally publishedYes

Keywords

  • DA receptors
  • Lithium
  • Striatal DOPAC
  • Supersensitivity
  • Tolerance

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