Length of continuous cocaine exposure determines the persistence of muscarinic and benzodiazepine receptor alterations

Abstract

The effects of varied durations of cocaine (1, 3 or 5 days) on muscarinic (MSC) and benzodiazepine (BZD) binding sites in striatum and hippocampus were investigated using homogenate receptor binding. The progressive alterations in these receptor sites from a 5 day cocaine administration were also examined 12 h, 2 days or 21 days after drug exposure. Neither a one nor a three day exposure to cocaine produced any long-term alteration in BZD binding in either structure whereas a 5 day administration produced significant increases in binding. Decreases in MSC receptor binding were apparent in striatum from either a 3 or 5 day cocaine exposure and in hippocampus from a 5 day exposure. The 5 day cocaine exposure produced immediate increases in striatal and hippocampal BZD binding which persisted for 21 days. Conversely, 5 days of cocaine produced a short-term increase in MSC receptor binding im both structures which then became significantly decreased 21 days later. Based on the divergent pattern of changes in BZD and MSC receptor types over time in these structures, it appears that cocaine may induce such changes via separate mechanisms. In addition, it is apparent that changes in the numbers of these receptor sites after cocaine exposure can be quite dynamic, changing rapidly over time.