Preexposure to drug administration context blocks the development of tolerance to sedative effects of diazepam

The development of tolerance to benzodiazepine (BDZ) and other psychoactive agents such as morphine, alcohol, and barbiturates is thought to be a cont ingent or learning phenomenon. In a previous report, we demonstrated a posi tive correlation between the development of tolerance to the sedative effec ts of diazepam (DZ) and hippocampal synaptic plasticity. The results of the present work show that the development of tolerance to the hypolocomotor a ction of DZ (5 mg/kg) for 4 days and the associated increase in synaptic pl asticity are context specific. Because animal preexposure to the drug admin istration context blocks both the tolerance sedative effects of DZ and the increased hippocampal synaptic plasticity, observed after 4 days of DZ admi nistration, we propose the increased synaptic plasticity on hippocampal dev elopment as one of the biological substrates to the tolerance to DZ. Beside s, the continuous administration of DZ did not induce a conditioning oppone nt response in these animals. (C) 1999 Elsevier Science Inc.