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.
- Research Organization:
- Armed Forces Radiobiology Research Institute, Bethesda, MD (USA)
- OSTI ID:
- 7151883
- Journal Information:
- Pharmacol., Biochem. Behav.; (United States), Vol. 29:2
- Country of Publication:
- United States
- Language:
- English
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DOPAMINE
RECEPTORS
NERVOUS SYSTEM DISEASES
RADIOINDUCTION
PROSTAGLANDINS
RADIOSENSITIVITY EFFECTS
BEHAVIOR
IN VITRO
PSYCHOTROPIC DRUGS
RADIATION DOSES
RATS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM AGENTS
DISEASES
DOSES
DRUGS
HYDROXY COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NEUROREGULATORS
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
RODENTS
SYMPATHOMIMETICS
VERTEBRATES
560152* - Radiation Effects on Animals- Animals