Dopaminergic regulation of striatal acetylcholine release: importance of D1 and N-methyl-D-aspartate receptors.
The dopaminergic regulation of striatal cholinergic activity was studied using in vivo microdialysis to measure interstitial concentrations of acetylcholine (ACh) and choline in the striata of freely moving rats. The quaternary acetylcholinesterase inhibitor neostigmine (100 nM) was included in the perfusion solution to increase the recovery of ACh. d-Amphetamine (2 mg/kg, s.c.) and nomifensine (5 mg/kg, s.c.) increased the concentration of ACh in the striatal dialysate by 40 to 60%. Interstitial choline concentrations were reduced by both drugs. Administration of the selective D1 receptor antagonist SCH 23390 (0.3 mg/kg, s.c.) decreased the concentration of ACh in the striatal dialysate by 15 to 20%; in contrast, the selective D2 antagonist raclopride (1 mg/kg, s.c.) increased striatal ACh release by 50 to 60%. Raclopride also briefly increased the extracellular concentration of choline. Raclopride blocked the increase in locomotor activity produced by d-amphetamine, but did not further enhance ACh release. In contrast, SCH 23390 completely antagonized the increases in locomotion and striatal ACh release produced by d-amphetamine. These results indicate that d-amphetamine increases ACh release in the striatum via a D1 receptor mechanism. Consistent with this hypothesis, the selective D1 receptor agonist CY 208-243 (1 mg/kg, s.c.) increased striatal ACh release by approximately 60%. In contrast, local application of CY 208-243 (10 microM) and SCH 23390 (10 microM) failed to alter ACh concentrations in the striatal dialysate. Inclusion of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (10 microM) in the striatal perfusion solution significantly attenuated the increase in striatal ACh release produced by systemic CY 208-243.(ABSTRACT TRUNCATED AT 250 WORDS)
Damsma
G
G
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Robertson
G S
GS
Tham
C S
CS
Fibiger
H C
HC
D000109:Acetylcholine / Q000378:metabolism*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018492:Dopamine Antagonists; D005110:Extracellular Space / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012457:Salicylamides / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D007211:Indoles; D010617:Phenanthridines; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D012457:Salicylamides; C054531:CY 208-243; D009627:Nomifensine; D020891:Raclopride; D016291:Dizocilpine Maleate; D000661:Amphetamine; D000109:Acetylcholine; D004298:Dopamine