Discriminative stimulus effects of esteratic local anesthetics in squirrel monkeys.
A number of esteratic local anesthetics serve as positive reinforcers and produce cocaine-like discriminative stimulus effects in animals. It has been suggested that the affinity of these compounds for a site on the dopamine transporter, and not their local anesthetic actions, is responsible for these abuse-related behavioral effects. In the present study, three local anesthetics previously shown to be self-administered in animals were examined in squirrel monkeys trained to discriminate cocaine (0.3 mg/kg) from saline in a two-lever, food-reinforced procedure. Dimethocaine (0.1-3.0 mg/kg) fully and dose-dependently substituted for cocaine. Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the dopamine D1 receptor antagonist SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine) and the dopamine D2 receptor antagonist raclopride (both at 0.003-0.03 mg/kg). SCH 39166 fully blocked the cocaine-like discriminative stimulus effects of dimethocaine and cocaine, but raclopride produced only partial antagonism of cocaine-lever selection. In addition, there was some evidence that raclopride blocked cocaine-lever responding produced by a lower dose of dimethocaine. In substitution studies, neither procaine (1-10 mg/kg) nor chloroprocaine (1-30 mg/kg) produced cocaine-like effects. These results support a role for dopamine in the behavioral effects of some local anesthetics.
Mansbach
R S
RS
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0310, USA.
Jortani
S A
SA
Balster
R L
RL
D062365:Aminobenzoates / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011412:Propanolamines / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D020891:Raclopride; D012044:Regression Analysis; D012453:Saimiri; D012457:Salicylamides / Q000008:administration & dosage / Q000494:pharmacology; D019966:Substance-Related Disorders
D062365:Aminobenzoates; D000779:Anesthetics, Local; D001552:Benzazepines; D002352:Carrier Proteins; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011412:Propanolamines; D012457:Salicylamides; C058081:ecopipam; D020891:Raclopride; D003042:Cocaine; C066888:dimethocaine; D004298:Dopamine