Use of negatively reinforcing electrical brain stimulation to detect conventional and nonconventional anxiolytics as well as an anxiogenic drug

The present study determined whether anxiolytics such as diazepam (DZP), th e benzodiazepine (BZD) receptor-selective agonist abecarnil (ABC), or the 5 -HT1(A) agent buspirone (BUS) would increase the response latency of rats t o switch-off electrical brain stimulation (EBS) of the periaqueductal gray (PAG). We also investigated the effects of pentyleneretrazole (PTZ), a purp orted anxiogenic. Given acutely, DZP (2.5 and 5 mg/kg, ip) and ABC (0.5 and I mg/kg, ip) increased response latency. The BZD receptor antagonist fluma zenil (10.0 mg/kg, ip) blocked these effects. Increasing the frequency of E BS reversed the effects of DZP and ABC, suggesting that motor disruption di d not account for the increase in latency seen with these drugs. Given acut ely, BUS (10.0 mg/kg, ip) also increased response latency, which was likely due to motor disruption because it was not reversed by increasing the freq uency of EBS. When BUS (2.5 mg/kg, ip) was given every 8 h for 3 days. an i ncrease in latency was also obtained, which was reversible by increasing th e frequency of EBS, Finally, PTZ (10 and 20 mg/kg, ip) shortened the latenc y to respond. These results (1) suggest that DZP, ABC, and chronic BUS atte nuate, whereas PTZ potentiates, the negative reinforcing stimulus (NRS) ind uced by FAG stimulation, and (2) support the hypothesis that the switch-off procedure accurately detects anxiolytic and anxiogenic drugs. (C) 2001 Els evier Science Inc. All rights reserved.