Chronic cocaine reduces alpha 2-adrenoceptor elicited mydriasis and inhibition of locus coeruleus neurons.
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.
Pitts
D K
DK
Neuroscience Laboratory, Wayne State University, Detroit, MI 48202.
Marwah
J
J
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D011680:Pupil / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; C060689:4-hydroxyclonidine; D003042:Cocaine; D003000:Clonidine