Chronic amphetamine alters D-2 but not D-1 agonist-induced behavioral responses in rats.
In two experiments, using different drug doses and periods of drug administration, rats were given amphetamine (AMPH) either continuously (via slow-release pellets), or intermittently (via injections). In both experiments, only the rats pretreated with intermittent AMPH subsequently showed heightened responsivity to the selective D-2 dopamine agonist LY171555 but not to SKF38393 (a D-1 agonist). This altered response to LY171555 was still present 30 days after the AMPH withdrawal, implying that D-2 dopamine receptors at least partially mediate AMPH inverse tolerance effects. The behavioral response to the D-2 agonist was clearly different in animals receiving high versus low doses of AMPH, suggesting that different drug-state learning may have occurred during pretreatment. In a third experiment, in which rats were given repeated daily injections of either the D-1 or the D-2 agonist, only rats pretreated with the D-2 agonist and subsequently injected with the D-2 agonist clearly showed heightened responsivity. These data imply an important role of D-2 receptors in the AMPH inverse tolerance effect.
Levy
A D
AD
Dept. of Psychology, U.C.L.A. 90024.
Kim
J J
JJ
Ellison
G D
GD
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D006120:Grooming / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*
D001552:Benzazepines; D003692:Delayed-Action Preparations; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000661:Amphetamine