Bozarth, M.A., Pudiak, C.M., & KuoLee, R. Predicting addiction
liability from brain stimulation reward data: I. A comparison of the acute
effects of cocaine, pseudoephedrine, nicotine, and caffeine. Manuscript
under editorial review.
Male, Long-Evans rats with lateral hypothalamic stimulating electrodes
were tested using a threshold-tracking procedure. This procedure determined
the minimum stimulation frequency (i.e., stimulation threshold) necessary
to maintain >30 presses/min during daily 30-min test sessions. Rats were
injected with cocaine hydrochloride (2.5 to 20 mg/kg, i.p.), pseudoephedrine
hydrochloride (3 to 100 mg/kg, i.p.), nicotine bitartrate (0.063 to 1 mg/kg,
s.c.), or caffeine (5 to 80 mg/kg, i.p.) immediately before testing. Peak
threshold-lowering effects were determined during 180-min test sessions.
Another series of tests compared the facilitatory effects produced by (i)
different nicotine bitartrate administration conditions (i.e., pH-adjusted
vs. pH-unadjusted solutions and s.c. vs. i.p. injection routes), (ii) nicotine
freebase in pH-adjusted and pH-unadjusted solutions, and (iii) repeated
nicotine bitartrate injections. These comparisons ensured that the most
effective nicotine administration parameters were used.
All compounds facilitated BSR. The prototypic addictive drug cocaine
lowered thresholds over twice as much as the nonaddictive compound pseudoephedrine.
This shows that BSR facilitation can be used to predict reinforcing drug
action, but quantitative measures of facilitation must be used to distinguish
drugs with high and low addiction liabilities. Nicotine’s facilitation
of BSR was quantitatively similar to that seen with pseudoephedrine and
markedly different from cocaine’s effect. Caffeine produced BSR facilitation
comparable to that seen with nicotine and with pseudoephedrine. Similar
peak-facilitation effects were seen with all nicotine administration conditions.
This suggests that even under optimal administration conditions, nicotine’s
profile in this animal model is that of a substance with a low addiction
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