Amphetamine behavioral sensitization and the excitatory amino acids.
The effects of 8 selective neuroeffector agonists and antagonists were measured in mice in order to identify specific functional changes associated with behavioral sensitization to amphetamine-induced stereotypy. The changes observed included a decreased convulsive threshold to N-methyl-DL-aspartic acid, an increased convulsive threshold to bicuculline, and an increased head-twitch response to 5-hydroxytryptophan. Of these effects, only the persistence of the two convulsive threshold changes correlated with the persistence of the behavioral sensitization. The induction of behavioral sensitization was blocked by haloperidol, dizocilpine or ketamine, but not affected by cyproheptadine or diazepam: therefore, the mechanism of the enhanced responsiveness involves not only a functional dopamine system, but also a functional N-methyl-D-aspartic acid component of the excitatory amino acid system. The block of behavioral sensitization also prevented the amphetamine-induced changes in the convulsive thresholds. Finally, neither ketamine nor dizocilpine affected the expression of the enhanced response in the behaviorally sensitized animals. The data indicate that the characteristics of amphetamine behavioral sensitization to stereotypy are similar to those of long-term potentiation.
Karler
R
R
Department of Pharmacology, University of Utah School of Medicine, Salt Lake City 84132.
Chaudhry
I A
IA
Calder
L D
LD
Turkanis
S A
SA
D000596:Amino Acids / Q000502:physiology*; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003533:Cyproheptadine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009451:Neuroeffector Junction / Q000187:drug effects; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects
D000596:Amino Acids; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D003533:Cyproheptadine; D007649:Ketamine; D016291:Dizocilpine Maleate; D000661:Amphetamine; D006220:Haloperidol; D003975:Diazepam