Research Article| Volume 21, ISSUE 4, P374-381, April 1986

Acute and chronic effects of haloperidol on plasma and brain homovanillic acid in the rat

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      The effects of acute and chronic administration of haloperidol on homovanillic acid (HVA) in plasma and the brain were examined in the rat. Acute haloperidol treatment (1 mg/kg) resulted in highly significant elevations in HVA within 30 min and produced a maximal increase of HVA in 3–6 hr in both plasma and the whole brain. The response of brain HVA to increasing doses (0.05–30 mg/kg) of haloperidol showed an inverted U pattern Plasma HVA showed a very flat response to lower doses (⩽ 5 mg/kg) of haloperidol and a dramatically elevated one to higher doses (⩾ 10 mg/kg). Haloperidol produced a parallel increase in plasma and brain HVA at lower doses (⩽ 2 mg/kg) only. After chronic administration of haloperidol for up to 28 days, the response of HVA in plasma correlated mainly with, but tolerated later than, those in the whole brain and the olfactory tubercle.
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        • Asper H
        • Baggiolini M
        • Burki HR
        • Lauener H
        • Ruch W
        • Stille G
        Tolerance phenomena with neuroleptics. Catalepsy, apomorphine stereotypies and striatal dopamine metabolism in the rat after single and repeated administration of loxapine and haloperidol.
        Eur J Pharmacol. 1973; 22: 287
        • Bacopoulos NG
        • Heninger GR
        • Roth RH
        Effects of haloperidol and probenecid on plasma and CSF dopamine metabolites in the rhesus monkey (Macacca mulatta).
        Life Sci. 1978; 23: 1805
        • Bacopoulos NG
        • Bustos G
        • Redmond DE
        • Baulu J
        • Roth RH
        Regional sensitivity of primate brain dopaminergic neurons to haloperidol: Alterations following chronic treatment.
        Brain Res. 1978; 157: 396
        • Bacopoulos NG
        • Hattox SE
        • Roth RH
        3,4-Dihydroxyphenylacetic acid and homovanillic acid in rat plasma: Possible indicators of central dopaminergic activity.
        Eur J Pharmacol. 1979; 56: 225
        • Bacopoulos NG
        • Redmond DE
        • Baulu J
        • Roth RH
        Chronic haloperidol or fluphenazine Effects on dopamine metabolism in brain, cerebrospinal fluid and plasma of Cercopithecus aethiops (vervet monkey).
        J Pharmacol Exp Ther. 1980; 212: 1
        • Bowers Jr, MB
        • Swigar ME
        • Jatlow PI
        • Goicoechea N
        Plasma catecholamine metabolites and early response to haloperidol.
        J Clin Psychiatry. 1984; 45: 248
        • Bunney BS
        • Walters JR
        • Roth RH
        • Aghajanian GK
        Dopaminergic neurons: Effect of antipsychotic drugs and amphetamine on single-cell activity.
        J Pharmacol Exp Ther. 1973; 185: 560
        • Carlsson A
        Antipsychotic drugs, neurotransmitters and schizophrenia.
        Am J Psychiatry. 1978; 135: 164
        • Chang WH
        • Scheinin M
        • Burns RS
        • Linnoila M
        Rapid and simple determination of homovanillic acid in plasma using high performance liquid chromatography with electrochemical detection.
        Acta Pharmacol Toxicol. 1983; 53: 275
        • Chang WH
        • Yeh EK
        • Hu WH
        • Tseng YT
        • Chung MC
        • Chang HF
        Pre-frontal cortex: Possible site of antipsychotic action of haloperidol.
        Biol Psychiatry. 1986; (Submitted to:) (submitted for publication).
        • Harris PQ
        • Brown SJ
        • Friedman MJ
        • Bacopoulos NT
        Plasma drug and homovanillic acid levels in psychotic patients receiving neuroleptics.
        Biol Psychiatry. 1984; 19: 849
        • Hyttel J
        Levels of HVA and DOPAC in mouse corpus striatum in the supersensitivity phase after neuroleptic treatment.
        J Neurochem. 1977; 28: 227
        • Julou L
        • Scatton B
        • Glowinski J
        Acute and chronic treatment with neuroleptics: Similarities and differences in their action on nigrastriatal, mesolimbic, and mesocortical dopaminergic neurons.
        Adv Biochem Psychopharmacol. 1977; 16: 617
        • Kendler KS
        • Davis KL
        Acute and chronic effects of neuroleptic drugs on plasma and brain homovanillic acid in the rat.
        Psychiatry Res. 1984; 13: 51
        • Kendler KS
        • Heninger GR
        • Roth RH
        Brain contribution to the haloperidol-induced increase in plasma homovanillic acid.
        Eur J Pharmacol. 1981; 71: 321
        • Lerner P
        • Nose P
        • Gorden EK
        • Lovenberg W
        Haloperidol: Effect of long-term treatment on rat striatal dopamine synthesis and turnover.
        Science. 1977; 197: 181
        • Matsumoto T
        • Uchimura H
        • Hirano M
        • Kern JS
        • Yokoo H
        • Shimomura M
        • Nakahara T
        • Inoue K
        • Oomagari K
        Differential effects of acute and chronic administration of haloperidol on homovanillic acid levels in discrete dopaminergic areas of rat brain.
        Eur J Pharmacol. 1983; 89: 27
        • Nyback H
        • Sedvall G
        Effect of chlorpromazine on accumulation and disappearance of catecholamines formed from tyrosine-C14 in brain.
        J Pharmacol Exp Ther. 1968; 162: 294
        • O'Keeffe R
        • Sharman DF
        • Vogt M
        Effect of drugs used in psychoses on cerebral dopamine metabolism.
        Br J Pharmacol. 1970; 38: 287
        • Scatton B
        • Glowinski J
        • Julou L
        Dopamine metabolism in the mesolimbic and mesocortical dopaminergic systems after single or repeated administrations of neuroleptics.
        Brain Res. 1976; 109: 184
        • Settle Jr, EC
        • Ayd Jr, FJ
        Haloperidol: A quarter century of experience.
        J Clin Psychiatry. 1983; 44: 440