Rh. Marin et al., Preexposure to drug administration context blocks the development of tolerance to sedative effects of diazepam, PHARM BIO B, 64(3), 1999, pp. 473-477
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.