Rs. Mansbach et al., DISCRIMINATIVE STIMULUS EFFECTS OF ESTERATIC LOCAL-ANESTHETICS IN SQUIRREL-MONKEYS, European journal of pharmacology, 274(1-3), 1995, pp. 167-173
A number of esteratic local anesthetics serve as positive reinforcers
and produce cocaine-like discriminative stimulus effects in animals. I
t has been suggested that the affinity of these compounds for a site o
n the dopamine transporter, and not their local anesthetic actions, is
responsible for these abuse-related behavioral effects. In the presen
t study, three local anesthetics previously shown to be self-administe
red in animals were examined in squirrel monkeys trained to discrimina
te cocaine (0.3 mg/kg) from saline in a two-lever, food-reinforced pro
cedure. Dimethocaine (0.1-3.0 mg/kg) fully and dose-dependently substi
tuted for cocaine. Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3
mg/kg) which produced full (> 80%) substitution for cocaine were admin
istered in combination with the dopamine D-1 receptor antagonist SCH 3
9166 ydroxy-N-methyl-5H-benzo[d]naphtho-(2,1-b)azepine) and the dopami
ne D-2 receptor antagonist raclopride (both at 0.003-0.03 mg/kg). SCH
39166 fully blocked the cocaine-like discriminative stimulus effects o
f dimethocaine and cocaine, but raclopride produced only partial antag
onism 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.