TY - JOUR
T1 - Only tyrosine-containing metabolites of [Leu]Enkephalin impair active avoidance conditioning in mice
AU - Janak, Patricia H.
AU - Martinez, Joe L.
N1 - Funding Information:
We thank Dr. Susan Weinberger for her editorial assistance. Supported by PHS National Research Service Award DA-5375-01 to P.H.J. from the National Institute on Drug Abuse, and PHS grant DA 04195 to J.L.M.Jr. also from the National Institute on Drug Abuse.
PY - 1990/12
Y1 - 1990/12
N2 - The effects of the enkephalin metabolites, Tyr, des-Tyr-[Leu]enkephalin (GGFL), and Tyr-Gly-Gly (YGG), on acquisition of an active avoidance task following their IP administration to mice were determined. Neither free Tyr (3.9-390.0 μg/kg) nor GGFL (7.1-710.0 μg/kg) altered acquisition of the avoidance response. In contrast, 53, but not 16 μg/kg, of YGG significantly impaired response acquisition. A 390.0, but not 39.0 μg/kg, dose of Tyr decreased locomotor activity levels measured in an open field. Together with previous findings that the enkephalin metabolites Tyr-Gly and Tyr-Gly-Gly-Phe also impair avoidance acquisition, these data indicate that the dipeptide Tyr-Gly is the minimum sequence needed to intefere with acquisition of an active avoidance response. Because the various enkephalin metabolites do not bind to opioid receptors, it is likely that their effects on avoidance acquisition represent a separate class of pharmacological agents whose effects are mediated by a nonopioid receptor mechanism. These results are important to the interpretation of behavioral studies involving peripheral administration of the opioid peptide, [Leu]enkephalin (LE).
AB - The effects of the enkephalin metabolites, Tyr, des-Tyr-[Leu]enkephalin (GGFL), and Tyr-Gly-Gly (YGG), on acquisition of an active avoidance task following their IP administration to mice were determined. Neither free Tyr (3.9-390.0 μg/kg) nor GGFL (7.1-710.0 μg/kg) altered acquisition of the avoidance response. In contrast, 53, but not 16 μg/kg, of YGG significantly impaired response acquisition. A 390.0, but not 39.0 μg/kg, dose of Tyr decreased locomotor activity levels measured in an open field. Together with previous findings that the enkephalin metabolites Tyr-Gly and Tyr-Gly-Gly-Phe also impair avoidance acquisition, these data indicate that the dipeptide Tyr-Gly is the minimum sequence needed to intefere with acquisition of an active avoidance response. Because the various enkephalin metabolites do not bind to opioid receptors, it is likely that their effects on avoidance acquisition represent a separate class of pharmacological agents whose effects are mediated by a nonopioid receptor mechanism. These results are important to the interpretation of behavioral studies involving peripheral administration of the opioid peptide, [Leu]enkephalin (LE).
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U2 - 10.1016/0091-3057(90)90542-P
DO - 10.1016/0091-3057(90)90542-P
M3 - Article
C2 - 2093169
AN - SCOPUS:0025636050
SN - 0091-3057
VL - 37
SP - 655
EP - 659
JO - Pharmacology, Biochemistry and Behavior
JF - Pharmacology, Biochemistry and Behavior
IS - 4
ER -