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Generalization tests with intraventricularly applied pro-enkephalin B-derived peptides in rats trained to discriminate the opioid kappa receptor agonist ethylketocyclazocine


Rats were trained in a two-lever food-reinforced procedure to discriminate between the effects of saline and the opioid kappa receptor agonist ethylketocyclazocine. After acquisition of this discrimination, generalization tests with opioid peptides such as β-endorphin, α-neoendorphin, dynorphin A and some dynorphin-derived peptides were conducted. The rats dose-dependently generalized the effects of intracerebroventricularly injected ethylketocyclazocine but not β-endorphin, α-neoendorphin, dynorphin A1–8, dynorphin A1–13, D-Cys2-L-Cys5-dynorphin A1–13 or dynorphin A.

D-Cys2-L-Cys5-dynorphin A1–13, in contrast to dynorphin A itself, dose-dependently caused analgesia and catatonia that was reversible with naloxone. Studies into the receptor preference of this derivative, using the technique of “selective tolerance”, revealed that this dynorphin derivative is almost devoid of kappa-receptor activity.

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Correspondence to Albert Herz.

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Shearman, G.T., Schulz, R., Schiller, P.W. et al. Generalization tests with intraventricularly applied pro-enkephalin B-derived peptides in rats trained to discriminate the opioid kappa receptor agonist ethylketocyclazocine. Psychopharmacology 85, 440–443 (1985).

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Key words

  • Drug discrimination
  • Ethylketocyclazocine
  • Dynorphin
  • Dynorphin derivatives
  • Rats