Faculty Collaboration Database

Effects of chronic nicotine treatment on the accumulation of [3H]tetraphenylphosphonium by cerebral cortical synaptosomes. J Neurochem 1993 Feb;60(2):687-95

Date

02/01/1993

Pubmed ID

8419544

DOI

10.1111/j.1471-4159.1993.tb03202.x

Scopus ID

2-s2.0-0027497595 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

Chronic exposure of rats to nicotine increases the number of [3H]nicotine binding sites in the brain; however, it is not clear whether nicotinic cholinergic receptor function is altered as well. In this study, we have used [3H]tetraphenylphosphonium as a probe of synaptosomal membrane potential to investigate whether exposure to nicotine in vivo alters the ability of cerebral cortical synaptosomes to maintain a potential difference and to depolarize in response to in vitro nicotine. Treatment of rats for 14 days with 0.475 mg of nicotine base/day via subcutaneously implanted minipumps resulted in a decrease in the synaptosomal accumulation of [3H]tetraphenylphosphonium in physiological buffer, corresponding to a decrease in estimated membrane potential from -55 mV to -50 mV. The onset of the decrease in membrane potential occurred after 7 days of in vivo nicotine treatment and was significantly correlated with an increase in [3H]nicotine binding to cerebral cortical synaptosomal (P2) membranes. Nicotine, at in vitro concentrations of 3-1,000 microM, decreased [3H]tetraphenylphosphonium accumulation in cerebral cortical synaptosomes from control animals. When compared to accumulation in buffer alone, in vitro nicotine and other nicotinic agonists did not significantly decrease [3H]tetraphenylphosphonium accumulation in cerebral cortical synaptosomes prepared from rats treated with nicotine in vivo. These studies provide evidence that chronic treatment with nicotine results in an average lower membrane potential in cerebral cortical synaptosomes and in functional down-regulation of the depolarization response to nicotinic cholinergic receptor stimulation.

Author List

Hillard CJ, Pounds JJ

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Binding Sites
Cell Membrane
Cerebral Cortex
Drug Administration Schedule
Kinetics
Male
Membrane Potentials
Nicotine
Onium Compounds
Organophosphorus Compounds
Rats
Rats, Sprague-Dawley
Synaptosomes
Time Factors
Tritium