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

1989; Elsevier BV; Volume: 160; Issue: 2 Linguagem: Inglês

10.1016/0014-2999(89)90492-5

1879-0712

David K. Pitts, Joe Marwah,

Pain Mechanisms and Treatments

The effects of chronic cocaine (50 mg/kg per day for two weeks) administration on two alpha 2-adrenoceptor-mediated responses were studied in rats. Chronic administration of cocaine significantly (compared to sham controls) attenuated the alpha 2-adrenoceptor-mediated inhibition of noradrenergic locus coeruleus (LC) neurons as well as alpha 2-adrenoceptor elicited mydriasis. Noradrenergic LC neurons from the cocaine treated and sham sham groups differed significantly in their responsiveness to the inhibitory effects of clonidine (ED50 values micrograms/kg: sham 7.35 +/- 1.13 and cocaine-treated 17.17 +/- 4.40, P less than 0.05). The ED50 values for the mydriatic response were sham 5.71 +/- 0.49 and cocaine-treated 16.42 +/- 0.69 micrograms/kg, respectively, P less than 0.001. No differences in cardiovascular responses to systemically injected clonidine between the chronic cocaine- and sham-treated groups were observed. Chronic cocaine treatment attenuates the two alpha 2-adrenoceptor-mediated responses most likely via an interaction with central catecholaminergic neurotransmission.