Failure of MK-801 to suppress D1 receptor-mediated induction of locomotor activity and striatal preprotachykinin mRNA expression in the dopamine-depleted rat

• Published in: Neuroscience Vol. 137; no. 2; pp. 505 - 517
• Main Authors: Campbell, B.M., Kreipke, C.W., Walker, P.D.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2006; Elsevier
• Subjects: 6-hydroxydopamine; Animals; basal ganglia; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - physiopathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Dizocilpine Maleate - pharmacology; Dopamine - deficiency; Dopamine Agonists - pharmacology; Down-Regulation - drug effects; Down-Regulation - physiology; Drug Synergism; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; hyperactivity disorder; locomotor activity; Male; Medical sciences; Motor Activity - drug effects; Motor Activity - physiology; Neurology; Oxidopamine; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - physiopathology; Parkinson’s disease; Protein Precursors - genetics; Rats; Receptors, Dopamine D1 - drug effects; Receptors, Dopamine D1 - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; RNA, Messenger - drug effects; RNA, Messenger - metabolism; substance P; Tachykinins - genetics; Up-Regulation - drug effects; Up-Regulation - physiology; Vertebrates: nervous system and sense organs; basal ganglia; DOPAC; M100907; hyperactivity disorder; 6-OHDA; MAPK; MK-801; 6-hydroxydopamine; CREB; SSPE; SKF 82958; ANOVA; PPT; NMDA; locomotor activity; substance P; 5-HT; DA; pERK; Parkinson’s disease; HPLC; HPLC-ED; Parkinson's disease; Rat; Central nervous system; Parkinson disease; Glutamate receptor; Oxidopamine; Neuropeptide; Degenerative disease; Antagonist; Nervous system diseases; Dopamine; Substance P; Dizocilpine; Rodentia; D1 Dopamine receptor; Corpus striatum; Basal ganglion; Catecholamine; Gene expression; Cerebral disorder; Locomotion; Vertebrata; Mammalia; Animal; Central nervous system disease; Neurotransmitter; NMDA receptor; Tachykinin; Extrapyramidal syndrome
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2005.09.024

N-methyl-
d-aspartate receptor antagonism exerts suppressive influences over dopamine D1 receptor-mediated striatal gene expression and locomotor behavior in the intact rat. The present study examined the effects of the
N-methyl-
d-aspartate receptor antagonist MK-801 on locomotor activity and striatal preprotachykinin mRNA expression stimulated by the D1 agonist (±)6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1
H-3-benzazepine hydrobromide in rats with bilateral dopamine lesions. Two months after neonatal dopamine lesions with 6-hydroxydopamine, rats were challenged with (±)6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1
H-3-benzazepine hydrobromide (1.0mg/kg) 15 min after administration of the
N-methyl-
d-aspartate receptor antagonist MK-801 (0.1mg/kg). In the intact rat, MK-801 prevented the induction of striatal preprotachykinin mRNA by D1 agonism. Similarly, direct infusion of (±)6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1
H-3-benzazepine hydrobromide (3.0μg) into the intact striatum produced an increase in locomotor activity that was suppressed by MK-801 (1.0μg) co-infusion. In the dopamine-depleted rat, MK-801 (0.1mg/kg) administered prior to (±)6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1
H-3-benzazepine hydrobromide (1.0mg/kg) increased, rather than suppressed, striatal preprotachykinin mRNA levels. Intrastriatal infusion of MK-801 (1.0μg) failed to inhibit D1-mediated induction of motor activity in dopamine-depleted animals. Together, these data provide further support that
N-methyl-
d-aspartate receptor antagonists lose their ability to block D1-mediated behavioral activation following dopamine depletion. The activation, rather than suppression, of tachykinin neurons of the direct striatonigral pathway may play a facilitatory role in this mechanism.