Role of dopaminergic mechanisms in the stimulatory effects of MK-801 injected into the ventral tegmental area and the nucleus accumbens.
The bilateral administration of 10 micrograms of (+)MK-801, but not (-)MK-801, into either the VTA or the N.Ac. stimulated locomotor activity. The stimulation induced by (+)MK-801 at both sites was inhibited by reserpine (5 mg/kg, SC) and the D1 antagonist, SCH 23390 (0.1 mg/kg, SC). Eticlopride (0.03 mg/kg, SC), a D2 antagonist, inhibited the stimulation produced by MK-801 in the VTA but not in the N.Ac. Baclofen (32 ng), a GABAB receptor agonist, injected into the VTA inhibited the stimulatory response to MK-801 injected systemically, into the VTA, or into the N.Ac., but did not significantly inhibit spontaneous locomotion or the stimulatory response to apomorphine (5 mg/kg, SC). These observations suggest that the stimulatory effects of MK-801 in the VTA and the N.Ac. are dependent on endogenous dopamine. In addition, the effects produced by MK-801 injected into the VTA closely resemble those produced by the systemic administration of low doses of MK-801, suggesting that this is the primary site of action of MK-801.
Narayanan
S
S
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus 43210, USA.
Willins
D
D
Dalia
A
A
Wallace
L
L
Uretsky
N
N
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D006651:Histocytochemistry; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D012457:Salicylamides / Q000494:pharmacology; D013268:Stimulation, Chemical; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000033:anatomy & histology / Q000201:enzymology / Q000502:physiology*
D018759:Adrenergic Uptake Inhibitors; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D012457:Salicylamides; D016291:Dizocilpine Maleate; D012110:Reserpine; D014446:Tyrosine 3-Monooxygenase; D001418:Baclofen; C045989:eticlopride; D001058:Apomorphine; D004298:Dopamine