Methamphetamine self-administration and the effect of contingency on monoamine and metabolite tissue levels in the rat.
A number of studies have shown that exposure to high doses of methamphetamine (MA) is toxic to central dopamine (DA) and serotonin (5-HT) neurons. In most of those studies, however, high doses of MA were experimenter-administered during a short exposure time. Because contingency is a determinant for many effects of drug exposure, the present objective was to investigate the effects of self-administered MA on tissue monoamine levels following a short (24 hours) or longer (7 days) withdrawal period. As previously reported, a noncontingent "binge" high-dose treatment regimen (4 injections of 10 mg/kg MA administered every 2 hours) produced persistent depletion of cortical 5-HT and striatal DA. Effects of self-administered MA (0.1 mg/kg/infusion) were then determined following a 20-day duration where a yoked design was employed such that some rats received MA contingent on an operant lever press and others received either MA or saline dependent on the responses of the contingent rat. Self-administered MA produced a transient striatal DA depletion with a more persistent increase in DA turnover, indicating the presence of some lasting adaptations. Furthermore, the yoked design revealed that there was no effect of contingency on these parameters.
Brennan
Katharine A
KA
Institute of Environmental Science and Research Ltd, P.O. Box 50-348, Porirua 5240, New Zealand. katie.brennan@damascene.net.nz
Colussi-Mas
Joyce
J
Carati
Caleb
C
Lea
Rod A
RA
Fitzmaurice
Paul S
PS
Schenk
Susan
S
D000818:Animals; D002404:Catheterization; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D011597:Psychomotor Performance; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012701:Serotonin / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome; D013997:Time Factors
D000697:Central Nervous System Stimulants; D012701:Serotonin; D008694:Methamphetamine; D004298:Dopamine