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Chronic cocaine reduces α2-adrenoceptor elicited mydriasis and inhibition of locus coeruleus neurons

Authors
Journal
European Journal of Pharmacology
0014-2999
Publisher
Elsevier
Publication Date
Volume
160
Issue
2
Identifiers
DOI: 10.1016/0014-2999(89)90492-5
Keywords
  • Locus Coeruleus
  • α2-Adrenoceptors
  • Mydriasis
  • Clonidine
  • Cocaine
Disciplines
  • Medicine

Abstract

Abstract The effects of chronic cocaine (50 mg/kg per day for two weeks) administration on two α 2-adrenoceptor-mediated responses were studied in rats. Chronic administration of cocaine significantly (compared to sham controls) attenuated the α 2-adrenoceptor-mediared inhibition of noradrenergic locus coeruleus (LC) neurons as well as α 2-adrenoceptor elicited mydriasis. Noradrenergic LC neurons from the cocaine treated and sham groups differed significantly in their responsiveness to the inhibitory effects of clonidine (ED 50 values μg/kg: sham 7.35 ± 1.13 and cocaine-treated 17.17 ± 4.40, P < 0.05). The ED 50 values for the mydriatic response were sham 5.71 ± 0.49 and cocaine-treated 16.42 ± 0.69 μg/kg, respectively, P < 0.001. No differences in cardiovascular responses to systematically injected clonidine between the chronic cocaine- and sham-treated groups were observed. Chronic cocaine treatment attenuates the two α 2-adrenoceptor-mediated responses most likely via an interaction with central catecholaminergic neurotransmission.

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