Behavioral changes and [123I]IBZM equilibrium SPECT measurement of amphetamine-induced dopamine release in rhesus monkeys exposed to subchronic amphetamine.
Previously we have shown that twelve weeks of repeated low-dose d-amphetamine (AMPH) exposure in rhesus monkeys induces a long-lasting enhancement of behavioral responses to acute low-dose challenge. The present study was designed to investigate the behavioral and neurochemical consequences of a six-week regimen of low-dose AMPH exposure (0.1-1.0 mg/kg, i.m., b.i.d.) in rhesus monkeys. SPECT imaging of AMPH's (0.4 mg/kg) ability to displace [123I]IBZM bound to D2 dopamine receptors in the striatum of saline control and AMPH-treated animals prior to and following chronic treatment was accomplished using a bolus/constant infusion paradigm. Following chronic AMPH treatment, all monkeys showed an enhanced behavioral response to acute AMPH challenge and a significant decrease in the percent of AMPH-induced displacement of [123I]IBZM in striatum compared to their pretreatment scans. These findings suggest that relatively small changes in presynaptic dopamine function may be reflected in significant alterations in the behavioral response to acute AMPH challenge.
Castner
S A
SA
Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
al-Tikriti
M S
MS
Baldwin
R M
RM
Seibyl
J P
JP
Innis
R B
RB
Goldman-Rakic
P S
PS
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008253:Macaca mulatta; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects; D015899:Tomography, Emission-Computed, Single-Photon
D001549:Benzamides; D018492:Dopamine Antagonists; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D003913:Dextroamphetamine; D004298:Dopamine