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.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1992|
ASJC Scopus subject areas
- Molecular Medicine