Dopamine-independent psychostimulant activity of a delta-agonist.
The effects of dopamine receptor agonists and antagonists on hyperlocomotion in mice induced by the nonpeptide delta-opioid receptor agonist (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide) (SNC80) were investigated. SNC80 significantly increased locomotion (maximally at 2 mg/kg). In antagonism tests, naltrindole and naltriben completely attenuated this SNC80-induced hyperlocomotion, which suggests that SNC80-induced hyperlocomotion may be mainly mediated through delta-opioid receptors. Although haloperidol (dopamine D2-receptor antagonist) did not affect SNC80-induced hyperactivity, it inhibited morphine-induced hyperlocomotion. In combination tests, SNC80, at a dose that did not affect spontaneous activity, significantly potentiated hyperlocomotion induced by methamphetamine and the dopamine D1-receptor agonist 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepin hydrobromide (SKF81297), whereas the combination of SNC80 and the D2-like receptor agonist 7-OH-N,N-di-n-propyl-2-aminotetralin did not affect locomotor activity. An earlier study demonstrated that the combination of the D1-receptor agonist SKF81297 and the D2-like receptor agonist 7-OH-N,N-di-n-propyl-2-aminotetralin synergistically induced hyperactivity in mice. Therefore, the present findings suggest that stimulation of either D2-like receptors or delta-opioid receptors can enhance the hyperlocomotion induced by stimulation of D1 receptors by methamphetamine and SKF81297, and the mechanism that underlies the hyperactivity caused by SNC80 may be different from that which underlies the effects of morphine.
Ito
Shinobu
S
Department of Legal Medicine, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
Mori
Tomohisa
T
Sawaguchi
Toshiko
T
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000819:agonists*
D001549:Benzamides; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; D010879:Piperazines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D009271:Naltrexone; D009020:Morphine; C055382:naltrindole; D006220:Haloperidol; D004298:Dopamine