TY - JOUR
T1 - Use of negatively reinforcing electrical brain stimulation to detect conventional and nonconventional anxiolytics as well as an anxiogenic drug
AU - Jung, M. E.
AU - Depoortere, R.
AU - Oglesby, M. W.
N1 - Funding Information:
This work was supported by USPHS grant AA 09378 (MWO).
PY - 2001
Y1 - 2001
N2 - The present study determined whether anxiolytics such as diazepam (DZP), the benzodiazepine (BZD) receptor-selective agonist abecarnil (ABC), or the 5-HT1A agent buspirone (BUS) would increase the response latency of rats to switch-off electrical brain stimulation (EBS) of the periaqueductal gray (PAG). We also investigated the effects of pentylenetetrazole (PTZ), a purported anxiogenic. Given acutely, DZP (2.5 and 5 mg/kg, ip) and ABC (0.5 and 1 mg/kg, ip) increased response latency. The BZD receptor antagonist flumazenil (10.0 mg/kg, ip) blocked these effects. Increasing the frequency of EBS reversed the effects of DZP and ABC, suggesting that motor disruption did not account for the increase in latency seen with these drugs. Given acutely, 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 frequency of EBS. When BUS (2.5 mg/kg, ip) was given every 8 h for 3 days, an increase in latency was also obtained, which was reversible by increasing the frequency of EBS. Finally, PTZ (10 and 20 mg/kg, ip) shortened the latency to respond. These results (1) suggest that DZP, ABC, and chronic BUS attenuate, whereas PTZ potentiates, the negative reinforcing stimulus (NRS) induced by PAG stimulation, and (2) support the hypothesis that the switch-off procedure accurately detects anxiolytic and anxiogenic drugs.
AB - The present study determined whether anxiolytics such as diazepam (DZP), the benzodiazepine (BZD) receptor-selective agonist abecarnil (ABC), or the 5-HT1A agent buspirone (BUS) would increase the response latency of rats to switch-off electrical brain stimulation (EBS) of the periaqueductal gray (PAG). We also investigated the effects of pentylenetetrazole (PTZ), a purported anxiogenic. Given acutely, DZP (2.5 and 5 mg/kg, ip) and ABC (0.5 and 1 mg/kg, ip) increased response latency. The BZD receptor antagonist flumazenil (10.0 mg/kg, ip) blocked these effects. Increasing the frequency of EBS reversed the effects of DZP and ABC, suggesting that motor disruption did not account for the increase in latency seen with these drugs. Given acutely, 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 frequency of EBS. When BUS (2.5 mg/kg, ip) was given every 8 h for 3 days, an increase in latency was also obtained, which was reversible by increasing the frequency of EBS. Finally, PTZ (10 and 20 mg/kg, ip) shortened the latency to respond. These results (1) suggest that DZP, ABC, and chronic BUS attenuate, whereas PTZ potentiates, the negative reinforcing stimulus (NRS) induced by PAG stimulation, and (2) support the hypothesis that the switch-off procedure accurately detects anxiolytic and anxiogenic drugs.
KW - Anxiogenic
KW - Anxiolytic
KW - Buspirone
KW - Diazepam
KW - Flumazenil
KW - Negative reinforcement
KW - Pentylenetetrazole
KW - Switch-off response
UR - http://www.scopus.com/inward/record.url?scp=0035077873&partnerID=8YFLogxK
U2 - 10.1016/S0091-3057(00)00435-4
DO - 10.1016/S0091-3057(00)00435-4
M3 - Article
C2 - 11274705
AN - SCOPUS:0035077873
VL - 68
SP - 33
EP - 42
JO - Pharmacology, Biochemistry and Behavior
JF - Pharmacology, Biochemistry and Behavior
SN - 0091-3057
IS - 1
ER -