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Functional reactivity of the dopaminergic system following acute and chronic ketamine treatments

Naunyn-Schmiedeberg's Archives of Pharmacology volume 378, pages 117–124 (2008)Cite this article

Abstract

This study examined the effects of acute (15 mg/kg, i.p.) and chronic subanesthetic (15 mg/kg, i.p., t.i.d, for 6 days) doses of ketamine [a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist] on amphetamine (presynaptic dopamine releasing agent; 10 mg/kg, i.p.) and apomorphine (a D2 receptor agonist; 1 mg/kg, i.p.)-induced stereotyped behaviors. The effect of acute and chronic ketamine on haloperidol (a D2 receptor antagonist; 1.6 mg/kg, i.p.)-induced catalepsy was also examined. Acute ketamine and chronic ketamine pretreatment increased amphetamine-induced stereotyped sniffing and locomotion compared with control groups. Acute ketamine significantly increased apomorphine-induced stereotyped sniffing. However, chronic ketamine had no significant effect on apomorphine-induced stereotyped sniffing. Acute, but not chronic ketamine treatment abolished haloperidol-induced catalepsy. The increase in amphetamine-induced stereotyped behaviors and the reversal of haloperidol-induced catalepsy by acute ketamine suggest that blockade of NMDA receptors by ketamine facilitates dopaminergic transmission. The absence of significant effect of chronic ketamine on apomorphine-induced stereotyped sniffing and haloperidol-induced catalepsy suggests that chronic ketamine does not modulate postsynaptic dopaminergic D2 receptors. It is suggested that chronic ketamine increased amphetamine-induced behaviors by causing hypersensitivity of presynaptic dopamine releasing mechanisms on dopaminergic terminals.

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Affiliations

  1. Department of Physiological Sciences and Department of Pharmacology, Obafemi Awolowo University, Ile-Ife, Nigeria

    A. R. Owolabi & O. E. Ukponmwan

  2. Department of Pharmacology, Obafemi Awolowo University, Ile-Ife, Nigeria

    M. A. Akanmu

  3. Department of Physiological Sciences, P.O. Box 1282, Ile-Ife, Osun State, Nigeria

    O. E. Ukponmwan

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  1. A. R. Owolabi
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  2. M. A. Akanmu
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  3. O. E. Ukponmwan
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Correspondence to O. E. Ukponmwan.

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Owolabi, A.R., Akanmu, M.A. & Ukponmwan, O.E. Functional reactivity of the dopaminergic system following acute and chronic ketamine treatments. Naunyn-Schmied Arch Pharmacol 378, 117–124 (2008). https://doi.org/10.1007/s00210-008-0283-x

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  • DOI: https://doi.org/10.1007/s00210-008-0283-x

Keywords

  • Stereotype behavior
  • Catalepsy
  • Ketamine
  • Amphetamine
  • Apomorphine
  • Rats