title: Sensitization of locus ceruleus neurons during withdrawal from chronic stimulants and antidepressants.
abstract: The effects of chronic exposure to cocaine, amphetamine and desipramine on noradrenergic neurons in the locus ceruleus were examined using intracellular recordings in rat brain slices. Animals were treated for 2 weeks with either cocaine, amphetamine or desipramine, and all recordings were made after a 1-week withdrawal period. Cells from all three drug-treated groups showed a significant increase in sensitivity to the acute effects of cocaine and amphetamine in prolonging the time course of the noradrenaline-mediated inhibitory postsynaptic potential. At the highest cocaine and amphetamine doses tested (10 and 3 microM, respectively), the inhibitory postsynaptic potential duration was increased approximately 233% in the drug-treated groups relative to saline controls. In addition, locus ceruleus neurons from the cocaine-, amphetamine- and desipramine-treated groups showed a significant 10, 12 and 17% increase, respectively, in the maximum outward current produced by clonidine. There was also a significant increase in the behavioral sensitivity of the drug-treated animals to the sedative effects of clonidine. The mechanisms responsible for the increased sensitivity to the acute effects of cocaine, amphetamine and alpha-2 agonists may play a role in the withdrawal response to psychostimulants.
authors.affiliation: Vollum Institute, Oregon Health Sciences University, Portland.
authors.forename: G C
authors.initials: GC
authors.lastname: Harris
authors.forename: J T
authors.initials: JT
authors.lastname: Williams
mesh_terms: D000661:Amphetamine / Q000009:adverse effects*; D000818:Animals; D003042:Cocaine / Q000009:adverse effects*; D003891:Desipramine / Q000009:adverse effects*; D004594:Electrophysiology; D007274:Injections, Intraperitoneal; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects; D013997:Time Factors
chemical_list: D000661:Amphetamine; D003042:Cocaine; D003891:Desipramine