Dopamine-N-methyl-D-aspartate interactions in the modulation of locomotor activity and memory consolidation in mice

Eur J Pharmacol. 1996 Jul 11;308(1):1-12. doi: 10.1016/0014-2999(96)00266-x.


This study explores the functional interaction between glutamatergic and dopaminergic systems in the modulation of two behavioral responses: locomotor activity and memory consolidation assessed with one-trial inhibitory avoidance. In agreement with previous reports, the NMDA receptor antagonist, (+)-MK-801 ((+)-5-methyl-10,11-dihydro(a,d) cyclohepten-5,10-imine hydrogen maleate), dose dependently enhanced locomotor activity in mice. The selective dopamine D1 receptor antagonist SCH 23390 at doses up to 0.05 mg/kg was unable to affect MK-801-induced locomotor activity, while (-)-sulpiride, but only at high doses (30 mg/kg), and haloperidol (0.05 mg/kg) blocked the MK-801 effect. Hypermotility induced by MK-801 was enhanced by repeated administration of haloperidol (once daily administration for 14 days of 4 mg/kg) or (-)-sulpiride (125 mg/kg), but not SCH 23390 (0.5 mg/kg). Dopamine D1 (SKF 38393)- and D2 (quinpirole)-selective agonists enhanced retention of one-trial inhibitory avoidance performance whilst NMDA receptor antagonists 3-(2-D-carboxypiperazin-4-yl)propyl-1-phosphoric acid (CPP) and MK-801 impaired it. Moreover we observed that the NMDA receptor antagonist-induced impairment of memory consolidation was attenuated by subeffective doses of SKF 38393 (5 mg/kg) and quinpirole (0.25 mg/kg). Impairment of the response induced by post-trial injections of CPP and MK-801, in the one-trial inhibitory avoidance test, was highly enhanced by 14 days of daily administration of haloperidol (4 mg/kg), sulpiride (25 mg/kg) but also SCH 23390 (0.5 mg/kg). These results suggest that different neural mechanisms underlie the functional interaction between the two neural systems in the modulation of these behavioral responses. Further, the results of the chronic study revealed a possible heterologous regulation of NMDA receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Animals
  • Avoidance Learning / drug effects
  • Benzazepines / pharmacology
  • Dizocilpine Maleate / pharmacokinetics
  • Dizocilpine Maleate / pharmacology
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Haloperidol / pharmacology
  • Male
  • Memory / drug effects*
  • Mice
  • Mice, Inbred Strains
  • Motor Activity / drug effects*
  • Piperazines / pharmacology
  • Quinpirole / pharmacology
  • Receptors, Dopamine / physiology*
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D2 / agonists
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Sulpiride / pharmacology


  • Benzazepines
  • Dopamine Agonists
  • Dopamine Antagonists
  • Excitatory Amino Acid Antagonists
  • Piperazines
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, N-Methyl-D-Aspartate
  • Quinpirole
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Dizocilpine Maleate
  • Sulpiride
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • Haloperidol