The effects of long-term, low-dose diazepam treatment on the guinea pig righting reflex and medial vestibular nucleus neuronal activity.
Guinea pigs received a 2 mg/kg IP injection of diazepam, or an equivalent volume of vehicle, daily for 28-60 days. To determine whether tolerance developed to the ataxic effects of diazepam on the righting reflex, daily righting reflex latency (RRL) measurements were made before and 20, 30, and 40 min following the diazepam or vehicle injection for 28 days. Analyses of the RRLs for individual animals indicated that a significant decrease in RRL over time (indicating tolerance) occurred in only one out of nine animals receiving diazepam and in none of the vehicle animals. Medial vestibular nucleus (MVN) neurons in brain stem slices from animals receiving chronic diazepam treatment had a significantly higher average firing rate than those from vehicle controls. These results suggest that: a) long-term treatment with single 2 mg/kg daily IP injections of diazepam does not result in tolerance to diazepam's ataxic effects on the righting reflex in the majority of animals; b) this form of diazepam treatment may, nonetheless, induce a hyperactivity of brain stem MVN neurons that may be consistent with the occurrence of a withdrawal syndrome.
Hutchinson
M A
MA
Department of Psychology, University of Otago, Dunedin, New Zealand.
Darlington
C L
CL
Smith
P F
PF
D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects*; D011897:Random Allocation; D011930:Reaction Time / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*; D014726:Vestibular Nuclei / Q000166:cytology / Q000187:drug effects*
D003975:Diazepam