TY - JOUR
T1 - Sensitization of locus ceruleus neurons during withdrawal from chronic stimulants and antidepressants
AU - Harris, G. C.
AU - Williams, J. T.
PY - 1992
Y1 - 1992
N2 - 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 μM, 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.
AB - 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 μM, 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.
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M3 - Article
C2 - 1578363
AN - SCOPUS:0026653906
SN - 0022-3565
VL - 261
SP - 476
EP - 483
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 2
ER -