Elsevier

Life Sciences

Volume 36, Issue 10, 11 March 1985, Pages 913-920
Life Sciences

Discriminative stimulus properties of methylxanthines and their metabolites in rats

https://doi.org/10.1016/0024-3205(85)90386-8Get rights and content

Abstract

Rats were trained to discriminate methylxanthines from saline under a two-lever concurrent variable ratio schedule of reinforcement. One group was trained to discriminate between saline and 32 mg/kg caffeine. A second group was trained to discriminate between 56 mg/kg theophylline and saline. Rats reliably discriminated between saline and the training methylxanthine, displaying graded generalization curves across training-drug doses. Caffeine-trained rats demonstrated caffeine-appropriate responding when tested with theophylline, paraxanthine, and 3-methylxanthine. Theobromine failed to generalize to the caffeine cue at test doses up to 75 g/kg. In contrast to the caffeine group, rats trained to discriminate theophylline from saline were less sensitive (higher ED50) to the effects of caffeine and paraxanthine test doses. Only partial generalization to the theophylline cue occured at paraxanthine doses up to 100 mg/kg. Based upon these data, it is suggested that the underlying substrate(s) for the caffeine cue is in some respects different from the substrate(s) for the theophylline cue.

References (14)

  • B. Berkowitz et al.

    Eur. J. Pharmac.

    (1970)
  • H.E. Modrow et al.

    Pharmac. Biochem. Behav.

    (1981)
  • M. Radulovacki et al.

    Brain Res.

    (1980)
  • M.J. Wayner et al.

    Pharmac. Biochem. Behav.

    (1976)
  • K. Ando

    Pharmac. Bioch. Behav.

    (1975)
  • M.J. Ornaud et al.
  • R.F. Bruns et al.
There are more references available in the full text version of this article.

Cited by (21)

  • Anti-obesity potential of natural methylxanthines

    2018, Journal of Functional Foods
    Citation Excerpt :

    Still, in other studies (Daly, Butts-Lamb, & Padgett, 1983; Fredholm, Irenius, Kull, & Schulte, 2001; Klotz et al., 1997) theophylline and paraxanthine were reported to have slightly higher affinities than caffeine for the A1R (in similar concentrations). On the other hand, theobromine does not possess the 1-methyl group and was described to have lower affinity for A1R and A2AR subtypes (Carney, Holloway, & Modrow, 1985; Schwabe, Ukena, & Lohse, 1985; Shi & Daly, 1999). Additionally, methylxanthines are also nonselective competitive inhibitors of phosphodiesterases at pharmacological doses (>1 mM) (Beavo et al., 1970; Butcher & Sutherland, 1962; Cardinali, 1980; Nicholson, Jackman, & Wilke, 1989).

View all citing articles on Scopus

H.E. Modrow is now at the U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010.

View full text