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obtained. Each dose-effect curve was analyzed using stan-
dard analysis of variance (ANOVA) and post-hoc testing to
determine significance of effects at individual doses.
Dr u g Discr im in a tion . Six adult male Sprague-Dawley
rats (Charles River, Wilmington, MA) were maintained at 350
g by postsession feeding. All subjects had unrestricted access
to water within a temperature-controlled animal-housing room
under a 12 h light/dark cycle. All testing was conducted during
the light phase.
Rats were studied in operant conditioning test chambers
(BRS/LVE, model RTC-022, Laurel, MD) which contained two
response keys. Responses were recorded as depressions of the
keys with a downward force of 0.2 N. Each response produced
an audible click when the house light and the stimulus lamps
over either lever were illuminated.
Experimental sessions were conducted at approximately the
same time daily, 5 days/week. Before each training session,
subjects received either saline or cocaine (10 mg/kg, ip) which
was given in a mixed sequence. When subjects received
cocaine, they were trained with food reinforcement to emit 20
consecutive responses on only one of the two response keys.
Food presentation was followed by a 20 s time out period
during which all stimulus lights were out and responses had
no scheduled consequences. When subjects received saline,
responses on the alternate key produced a food pellet according
to the same schedule. Injections were given 5 min before
sessions started. Sessions ended after 20 food presentations
or 15 min, whichever occurred first. Since subjects had been
trained previously, no further training was necessary prior to
conducting test sessions, in which the effects of various doses
of cocaine or test compounds were examined. Test sessions
were conducted after each two training sessions and were
identical with those training sessions with the exception that
20 consecutive responses on either of the response keys
produced a food pellet. Subjects were injected ip with one of
several doses of cocaine or test compound. Each dose was
typically examined once in each subject. Test sessions were
conducted if subjects met criteria of emitting greater than 85%
correct responses in the entire session and before the first food
pellet in each of the two training sessions preceding the test
session. When subjects failed to meet the criteria, training
continued until they did so for two consecutive sessions before
testing resumed.
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Ack n ow led gm en t. R.K. was supported by a NIDA-
sponsored National Research Council Fellowship. We
thank J ulie Haak, Sean Carter, and Brett Heller for
expert technical assistance. Animals used in this study
were maintained in facilities fully accredited by the
American Association for the Accreditation of Labora-
tory Animal Care (AAALAC), and all experimentation
was conducted according to the guidelines of the Insti-
tutional Care and Use Committee of the Intramural
Research Program, National Institute on Drug Abuse,
NIH, and the Guide for Care and Use of Laboratory
Animal Resources, National Research Council, Depart-
ment of Health, Education and Welfare, Publication
(NIH) 85-23, revised 1985.
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inhibitors on behavioral and toxic effects of cocaine. In Problems
of Drug Dependence 1993; Harris, L. S., Ed.; NIDA Monograph
141; NIDA: Washington, DC, 1994; p 441.
(21) Katz, J . L.; Izenwasser, S.; Allen, A. C.; Newman, A. H.
Behavioral Effects of Novel 4′- and 4′,4′′-substituted-3R-(diphen-
ylmethoxy)tropane Analogs. Soc. Neurosci. Abstr. 1994, 20, 1628
(No. 664.19). Newman, A. H.; Kline, R. H.; Allen, A. C.;
Izenwasser, S.; Katz, J . L. Novel 4′,4′′-substituted-3R-(diphen-
ylmethoxy)tropane Analogs are Potent and Selective Dopamine
Uptake Inhibitors. Soc. Neurosci. Abstr. 1994, 20, 1628 (No.
664.20).
(22) He, X. S.; Raymon, L. P.; Mattson, M. V.; Eldefrawi, A. E.; de
Costa, B. R. Further studies of the structure-activity relation-
ships of 1-[1-(2-benzo[b]thienyl)cyclohexyl]piperidine. Synthesis
and evaluation of 1-[1-(2-benzo[b]thienyl)N,N-dialkylcyclohexyl
amines] at dopamine uptake and phencyclidine binding sites.
J . Med. Chem. 1993, 36, 4075-4081.
(23) Rothman, R. B.; Becketts, K. M.; Radesca, L. R.; de Costa, B.
R.; Rice, K. C.; Carroll, F. I.; Dersch, C. M. Studies of the biogenic
amine transporters. II. A brief study on the use of [3H]DA-
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