Rotational behavior mediated by dopaminergic and nondopaminergic mechanisms after intranigral microinjection of specific mu, delta and kappa opioid agonists.
The regulation of motor behavior by mu, delta and kappa opiate receptors in the substantia nigra was examined. Unilateral microinjections of specific mu (DAGO), delta (DPDPE) and kappa (U-50,488H) ligands into the substantia nigra pars reticulata of rats produced dose-dependent contralateral turning. The opiate antagonist naloxone blocked these effects, suggesting that the circling was mediated through opiate receptors. The involvement of midbrain dopaminergic systems in this behavior was tested in two ways. Unilateral 6-hydroxydopamine lesions of the medial forebrain bundle decreased the circling produced by DPDPE and DAGO but increased the circling produced by U-50,488H. In contrast, activating dopaminergic systems with systemic injections of amphetamine increased the circling produced by DAGO and DPDPE but had no effect on the circling produced by U-50,488H. These findings suggest that kappa opioids exert opposite effects on locomotion: motor activation through the SNR and motor inhibition through actions in the SNC. Furthermore, the data suggest that the actions of kappa opioids in the SNC are opposite to those produced by mu and delta opioids.
Matsumoto
R R
RR
Department of Psychology, Brown University, Providence, Rhode Island.
Brinsfield
K H
KH
Patrick
R L
RL
Walker
J M
JM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D016627:Oxidopamine; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012399:Rotation
D004745:Enkephalins; D006892:Hydroxydopamines; D009294:Narcotics; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; D016627:Oxidopamine; D000661:Amphetamine