N-Oleoyl Alanine

Animal models

Preparation Method

To test the effects of N-Oleoyl Alanine on nicotine reward, an unbiased conditioned place preference (CPP) model was used. CPP was conducted in a linear series of three interconnected chambers, consisting of two large conditioning chambers that differed in color (black or white) and floor texture (white mesh or black rod) (20 × 20 × 20cm), separated by a smaller gray chamber. On the first day, subjects (n=8/group) were confined to the middle gray chamber for 5min to acclimate before being allowed access to all three chambers for 15min. The time spent in each chamber was recorded to test for potential baseline preferences. Prior to conditioning, there were no systematic biases in baseline preferences for the chambers among the groups. On days 2-4, mice underwent 20-minute conditioning sessions twice daily, 4h apart, conducted by the same investigator. After administration of saline or nicotine, the mice were confined to one of the large chambers. The control group received saline paired with both large chambers, while the nicotine group received nicotine in one large chamber and saline in the other large chamber. The chamber paired with nicotine was randomized for each subject, and treatments were counterbalanced so that half of the mice received nicotine in the morning and saline in the afternoon, while the other half received saline in the morning and nicotine in the afternoon. A maximum dose of 30mg/kg N-Oleoyl Alanine was assessed in CPP, as this dose of N-Oleoyl Alanine was effective in attenuating nicotine-induced CPP. Fifteen minutes before subcutaneous administration of nicotine (0.5mg/kg) or saline, N-Oleoyl Alanine (5, 15, 30mg/kg) or vehicle was administered intraperitoneally (n=8/group), which was 5min before the start of the conditioning session. On the test day (day 5), mice did not receive any injections but were placed in the center chamber with free access to both conditioning chambers during the 20-minute session. A preference score was determined by subtracting the time spent in the drug-paired side during the baseline day from the time spent in the drug-paired side during the test day.

Dosage form

Applications

References:
[1] Karin KN, Mustafa MA, Poklis JL, et al. N-oleoyl alanine attenuates nicotine reward and spontaneous nicotine withdrawal in mice. Drug Alcohol Depend. 2024 Jun 1;259:111276.