Effect of intranigral injections of dynorphin, dynorphin fragments and alpha-neoendorphin on rotational behaviour in the rat.
Peptides deriving from the proenkephalin B precursor were studied in the Ungerstedt rotational model after their unilateral injection into the substantia nigra. Dynorphin (DYN)-(1-17), DYN-(1-13) and DYN-(1-8) in 0.1-10 micrograms doses induced marked contralateral rotation. This effect was enhanced by subsequent systemic administration of D-amphetamine and blocked by previous treatment with naloxone. alpha-Neoendorphin produced similar effects although there was no evidence for dose-dependency. DYN-(6-17) which lacks opioid activity also produced contralateral rotation, which, however, was not naloxone reversible and D-amphetamine given subsequently did not induce asymmetric activation. Methionine enkephalin and leucine enkephalin, deriving from the proenkephalin A precursor were tested for comparison. Only the former produced weak contralateral rotation. GABA injected at the same site as DYN-(1-17) also induced contralateral rotation which was mimicked by nanogram doses of the gabaergic agonist muscimol. These findings suggest an interaction between peptides from the proenkephalin B precursor and nigro-striatal dopamine neurons as well as gabaergic striato-nigral efferents and/or interneurons.
D000818:Animals; D003913:Dextroamphetamine / Q000494:pharmacology; D004399:Dynorphins / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000494:pharmacology; D006801:Humans; D007120:Immunochemistry; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D004723:Endorphins; D010446:Peptide Fragments; D011498:Protein Precursors; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine; C025681:alpha-neoendorphin; D004399:Dynorphins; D003913:Dextroamphetamine