Attenuation of phenobarbital-induced deficits in coordinated locomotion during subacute exposure.
The effects of phenobarbital on coordinated locomotion were measured in rats trained to criterion to avoid electric shock by running treadmill fashion along a motor driven belt. Two phenobarbital groups (35 and 50 mg/kg) and saline controls were injected for 29 consecutive days. Testing was carried out on Drug Days 1, 15, and 29. On Drug Day 1, disturbances in gait and balance were reflected by an increased time off belt for the phenobarbital groups. In addition, both groups demonstrated a significant improvement in performance over the three 2-min trial test sessions. Deficits were further reduced on Drug Day 15, and by Drug Day 29, the performance of rats treated with 35 mg/kg was equivalent to control values while that of the 50 mg/kg group had improved by more than 90%. There was no corresponding change in plasma levels of phenobarbital during subacute dosing. After a one month drug withdrawal period, treatment with phenobarbital again produced coordination deficits which were equivalent to those seen on Drug Day 1. These data demonstrate that an attenuation of the effects of phenobarbital on coordination can begin within minutes of the initial test session and is most likely due to behavioral processes (i.e., acute functional tolerance). In addition, results suggest that further drug exposure may play a role in the carry-over of functional tolerance from one drug test session to the next.
D000704:Analysis of Variance; D000818:Animals; D004361:Drug Tolerance; D005260:Female; D009043:Motor Activity / Q000187:drug effects*; D010634:Phenobarbital / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010634:Phenobarbital