Similar behavioral and biochemical effects of long-term haloperidol and caerulein treatment in albino mice.
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.
Vasar
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E
Laboratory of Psychopharmacology, Tartu University, Estonia, USSR.
Allikmets
L
L
Soosaar
A
A
Lang
A
A
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002108:Ceruletide / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects*; D005442:Flumazenil / Q000494:pharmacology; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D013997:Time Factors
D009118:Muscimol; D005442:Flumazenil; D002108:Ceruletide; D000661:Amphetamine; D006220:Haloperidol