Article date: 1990/4/1
PubMed ID: 2111914
Journal name: Pharmacology, biochemistry, and behavior (ISSN: 0091-3057)
Behavioral and biochemical experiments on male albino mice have revealed similar effects after the cessation of repeated (15 days) haloperidol (0.5 mg/kg daily IP) and caerulein (0.1 mg/kg daily SC) treatment. Tolerance developed to the action of muscimol (a GABA-A agonist, 1 mg/kg IP), caerulein (a CCK-8 agonist, 15 micrograms/kg SC) and flumazenil (a benzodiazepine antagonist, 10 mg/kg IP). Muscimol and caerulein were not able to suppress the motor activity of mice after 15 days treatment with haloperidol and caerulein. Flumazenil, which increased motor activity in saline-treated animals, also failed to affect activity after extended haloperidol or caerulein treatment. In contrast, the motor excitation induced by amphetamine (an indirect dopamine agonist, 3 mg/kg IP) was increased after haloperidol or caerulein administration. In radioligand binding studies the density of dopamine-2-receptors in striatum, opioid receptors in mesolimbic structures, and benzodiazepine and GABA-A receptors in brainstem was significantly elevated after long-term haloperidol or caerulein treatment. Simultaneously, the number of CCK-8, benzodiazepine and GABA-A receptors in cerebral cortex was decreased. It is probable that CCK-8-ergic mechanisms are involved closely in the action of repeated haloperidol treatment. CCK-8 seems to modulate the action of haloperidol through altering the sensitivity of dopamine, opioid, GABA-A and benzodiazepine receptors.
Author List: Vasar E, Allikmets L, Soosaar A, Lang A
Publication Types: Comparative Study; Journal Article
Substances mentioned in the article: Muscimol; Flumazenil; Ceruletide; Amphetamine; Haloperidol;
Mesh terms: Amphetamine/pharmacology; Animals; Brain/drug effects; Ceruletide/administration & dosage; Drug Interactions; Exploratory Behavior/drug effects; Flumazenil/pharmacology; Haloperidol/administration & dosage; Male; Mice; Muscimol/pharmacology; Time Factors;