Effects of N-n-propylnorapomorphine enantiomers on single unit activity of substantia nigra pars compacta and ventral tegmental area dopamine neurons.
Prompted by conflicting reports of both agonist and antagonist properties of the S-(+)-enantiomer of the potent dopamine agonist R-(-)-N-n-propylnorapomorphine (NPA), we carried out extracellular, single unit recording studies to compare the effects of both enantiomers on substantia nigra and ventral tegmental area (VTA) dopamine neurons in male rats anesthetized with chloral hydrate. Like the classic dopamine agonist apomorphine, R-(-)-NPA inhibited cell firing in both populations. Mean cumulative doses to inhibit firing by 50% (ID50) were 0.53 micrograms/kg for nigral and 0.50 micrograms/kg for VTA dopamine cells, respectively, reflecting a potency for R-(-)-NPA 10-fold greater than that of apomorphine for inhibition of nigral dopamine cells (ID50 5.3 micrograms/kg). Inhibitions elicited by R-(-)-NPA could be fully reversed by i.v. haloperidol (0.2 mg/kg) but not by S-(+)-NPA in doses up to 0.9 mg/kg. Interestingly, S-(+)-NPA also exhibited agonist activity in both cell groups but with a much lower potency than R-(-)-NPA. In addition, VTA dopamine cells displayed a significantly greater sensitivity to the drug: ID50 values of 149 micrograms/kg vs. 514 micrograms/kg for VTA and substantia nigra neurons, respectively (P less than .01). Prior administration of haloperidol (0.1 mg/kg) consistently and fully prevented the inhibitory effects of S-(+)-NPA on all cells tested, although subsequent administration of haloperidol (up to 1.6 mg/kg) did not reverse completely S-(+)-NPA-induced inhibitions in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Cox
R F
RF
Pharmacology Section, Northeastern University College of Pharmacy and Allied Health Professions, Boston, Massachusetts.
Neumeyer
J L
JL
Waszczak
B L
BL
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013237:Stereoisomerism; D013378:Substantia Nigra / Q000187:drug effects*; D013681:Tegmentum Mesencephali / Q000187:drug effects*
D000978:Antiparkinson Agents; D011954:Receptors, Dopamine; C009074:N-n-propylnorapomorphine; D001058:Apomorphine