Radiation-induced increases in sensitivity of cataleptic behavior to haloperidol: possible involvement of prostaglandins.
The effects of radiation exposure on haloperidol-induced catalepsy were examined in order to determine whether elevated prostaglandins, through an action on dopaminergic autoreceptors, could be involved in the radiation-induced increase in the potency of this neuroleptic. Cataleptic behavior was examined in animals irradiated with various doses of gamma photons (1-150 Gy) and pretreated with a subthreshold dose of haloperidol (0.1 mg/kg). This approach was chosen to maximize any synergistic effects of radiation and haloperidol. After irradiation with doses less than or equal to 30 Gy, the combined treatment of haloperidol and radiation produced catalepsy, whereas neither treatment alone had an effect. This observed catalepsy could be blocked with prior administration of indomethacin, a prostaglandin synthesis inhibitor. Animals exposed to doses of radiation less than or equal to 50 Gy and no haloperidol, however, displayed apparent catalepsy. This effect was also antagonized by indomethacin. Prostaglandins can induce catalepsy and when administered in subthreshold doses along with subthreshold doses of haloperidol, catalepsy was observed. In order to assess a possible action of prostaglandins and radiation on dopaminergic activity, the functioning of striatal dopaminergic autoreceptors was examined by determining the effects of varying concentrations of haloperidol on the K+-evoked release of dopamine from striatal slices obtained from parallel groups of animals treated as above. Results indicated that sensitivity to haloperidol increased (higher K+-evoked dopamine release) in slices from irradiated or prostaglandin-treated animals and that this increase in sensitivity was blocked by indomethacin. Results from both experiments suggest that radiation-induced increases in endogenous neuronal mediators, such as prostaglandins, can induce catalepsy through an action on dopaminergic autoreceptors.
Joseph
J A
JA
Behavioral Sciences Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814-5145.
Kandasamy
S B
SB
Hunt
W A
WA
Dalton
T K
TK
Stevens
S
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000528:radiation effects*; D002375:Catalepsy / Q000209:etiology* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004298:Dopamine / Q000378:metabolism; D005720:Gamma Rays; D006220:Haloperidol / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D011453:Prostaglandins; D011189:Potassium Chloride; D006220:Haloperidol; D004298:Dopamine