Tolerance to catalepsy following chronic haloperidol is not associated with changes in GABA release in the globus pallidus.
In vivo microdialysis was used to investigate the relationship between extracellular GABA levels in rat globus pallidus following acute (1st injection) and chronic (29th injection) haloperidol (Hal) (0.25 mg kg-1 day-1, s.c.) with the presence and absence of catalepsy, respectively. There was no difference in basal pallidal GABA levels in the drug naive and chronically treated rats. Furthermore, pallidal GABA release was not affected following injection with Hal in either group although there was a prolonged catalepsy in the drug naive group and a tolerance to catalepsy in the chronically treated group. A previous microdialysis study employing similar experiment protocol showed that Hal increases striatal GABA release in drug naive rats and increases basal striatal GABA levels following chronic treatment. The results of the current study demonstrate that these effects are not reflected in the globus pallidus and suggest that striatal GABA interneurons and/or GABA projection neurons to extrapallidal nuclei such as the substantia nigra pars reticulata may be involved in initiating catalepsy following acute Hal and mediating the tolerance to catalepsy observed following chronic Hal.
O'Connor
W T
WT
Department of Pharmacology, Karolinska Institute, S171-77, Stockholm, Sweden.
Osborne
P G
PG
Ungerstedt
U
U
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced*; D004361:Drug Tolerance; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014150:Antipsychotic Agents; D005680:gamma-Aminobutyric Acid; D006220:Haloperidol