Effect of microinjections of apamin into the A10 dopamine region of rats: a behavioral and neurochemical analysis.
Hyperpolarization of dopamine neurons by activation of D2 and gamma-aminobutyric acidB 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.
Steketee
J D
JD
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman.
Kalivas
P W
PW
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001030:Apamin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001514:Bee Venoms / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000378:metabolism; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D001514:Bee Venoms; D015102:3,4-Dihydroxyphenylacetic Acid; D001030:Apamin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D004298:Dopamine