Effect of microinjections of apamin into the A10 dopamine region of rats

A behavioral and neurochemical analysis

Jeffery Steketee, P. W. Kalivas

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Hyperpolarization of dopamine neurons by activation of D2 and γ-aminobutyric acid(B) receptors involves an increased conductance of K+ ions. Apamin, a blocker of Ca2+-activated K+ channels, has been reported to increase activity of dopamine neurons. Increased activity of the mesolimbic dopamine system is associated with increased motor activity. Thus, we investigated the behavioral and neurochemical effects of acute and daily microinjections of apamin into the A10 region of the rat. Apamin increased motor activity in a dose-dependent manner, and this effect was blocked by pretreatment with 0.1 mg/kg haloperidol. In postmortem analysis, 6.0 pmol of apamin significantly increased the levels of dihydroxyphenylacetic acid in the A10 region and of dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens, and 2.0 pmol of apamin significantly increased the level of dopamine in the prefrontal cortex. In vivo dialysis in the nucleus accumbens of freely moving rats revealed that apamin elevated extracellular dopamine metabolites. Rats receiving daily microinjections of apamin into the A10 region did not exhibit an augmentation in motor activity, suggesting that rats did not become sensitized to chronic treatment. These data are discussed in terms of the role of apamin-sensitive dopamine mechanisms in motor behavior and sensitization of these motor behaviors.

Original languageEnglish (US)
Pages (from-to)711-719
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume254
Issue number2
StatePublished - 1990
Externally publishedYes

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Apamin
antineoplaston A10
Microinjections
Dopamine
Motor Activity
Dopaminergic Neurons
Nucleus Accumbens
Aminobutyrates
Calcium-Activated Potassium Channels
Homovanillic Acid
Acids
Haloperidol
Prefrontal Cortex
Dialysis
Ions

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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abstract = "Hyperpolarization of dopamine neurons by activation of D2 and γ-aminobutyric acid(B) receptors involves an increased conductance of K+ ions. Apamin, a blocker of Ca2+-activated K+ channels, has been reported to increase activity of dopamine neurons. Increased activity of the mesolimbic dopamine system is associated with increased motor activity. Thus, we investigated the behavioral and neurochemical effects of acute and daily microinjections of apamin into the A10 region of the rat. Apamin increased motor activity in a dose-dependent manner, and this effect was blocked by pretreatment with 0.1 mg/kg haloperidol. In postmortem analysis, 6.0 pmol of apamin significantly increased the levels of dihydroxyphenylacetic acid in the A10 region and of dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens, and 2.0 pmol of apamin significantly increased the level of dopamine in the prefrontal cortex. In vivo dialysis in the nucleus accumbens of freely moving rats revealed that apamin elevated extracellular dopamine metabolites. Rats receiving daily microinjections of apamin into the A10 region did not exhibit an augmentation in motor activity, suggesting that rats did not become sensitized to chronic treatment. These data are discussed in terms of the role of apamin-sensitive dopamine mechanisms in motor behavior and sensitization of these motor behaviors.",
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T1 - Effect of microinjections of apamin into the A10 dopamine region of rats

T2 - A behavioral and neurochemical analysis

AU - Steketee, Jeffery

AU - Kalivas, P. W.

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N2 - Hyperpolarization of dopamine neurons by activation of D2 and γ-aminobutyric acid(B) receptors involves an increased conductance of K+ ions. Apamin, a blocker of Ca2+-activated K+ channels, has been reported to increase activity of dopamine neurons. Increased activity of the mesolimbic dopamine system is associated with increased motor activity. Thus, we investigated the behavioral and neurochemical effects of acute and daily microinjections of apamin into the A10 region of the rat. Apamin increased motor activity in a dose-dependent manner, and this effect was blocked by pretreatment with 0.1 mg/kg haloperidol. In postmortem analysis, 6.0 pmol of apamin significantly increased the levels of dihydroxyphenylacetic acid in the A10 region and of dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens, and 2.0 pmol of apamin significantly increased the level of dopamine in the prefrontal cortex. In vivo dialysis in the nucleus accumbens of freely moving rats revealed that apamin elevated extracellular dopamine metabolites. Rats receiving daily microinjections of apamin into the A10 region did not exhibit an augmentation in motor activity, suggesting that rats did not become sensitized to chronic treatment. These data are discussed in terms of the role of apamin-sensitive dopamine mechanisms in motor behavior and sensitization of these motor behaviors.

AB - Hyperpolarization of dopamine neurons by activation of D2 and γ-aminobutyric acid(B) receptors involves an increased conductance of K+ ions. Apamin, a blocker of Ca2+-activated K+ channels, has been reported to increase activity of dopamine neurons. Increased activity of the mesolimbic dopamine system is associated with increased motor activity. Thus, we investigated the behavioral and neurochemical effects of acute and daily microinjections of apamin into the A10 region of the rat. Apamin increased motor activity in a dose-dependent manner, and this effect was blocked by pretreatment with 0.1 mg/kg haloperidol. In postmortem analysis, 6.0 pmol of apamin significantly increased the levels of dihydroxyphenylacetic acid in the A10 region and of dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens, and 2.0 pmol of apamin significantly increased the level of dopamine in the prefrontal cortex. In vivo dialysis in the nucleus accumbens of freely moving rats revealed that apamin elevated extracellular dopamine metabolites. Rats receiving daily microinjections of apamin into the A10 region did not exhibit an augmentation in motor activity, suggesting that rats did not become sensitized to chronic treatment. These data are discussed in terms of the role of apamin-sensitive dopamine mechanisms in motor behavior and sensitization of these motor behaviors.

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