Dopamine uptake inhibition is positively correlated with cocaine-induced stereotyped behavior

Abstract

Fast-scan cyclic voltammetry on freely moving rats was used to determine whether a correlation exists between the increase in stereotyped behavior and dopamine (DA) uptake inhibition following cocaine (20 mg/kg, i.p.) administration. Voltammetric recordings were performed every 100 ms at a carbon fiber microelectrode, positioned in the nucleus accumbens. The present experiments revealed that the time course of the changes in K(m) strictly parallels the time course of the increase in stereotypy after cocaine. More importantly, the magnitudes of cocaine-stimulated stereotypy were positively and significantly correlated with the K(m) increases. Therefore, these data closely link the DA transporter inhibition with cocaine-induced stereotypy.

Figure 1

Representative traces of electrically evoked DA signals detected by FSCV in rat NAc core before and 10 min after cocaine (20 mg/kg, i.p.) injection. These signals had an oxidation peak at +0.6 V and a reduction peak at -0.2 V vs. Ag/AgCl reference, identifying the released species as DA.

Figure 2

Effect of cocaine on the apparent Michaelis-Menten rate constant for DA uptake (K_m) (A) and stereotyped behavior of rats (B). Three pretreatment points were collected and then saline or cocaine (20 mg/kg, i.p.) was administrated. The time of drug administration is indicated by the arrow. *P<0.001. Data are mean ± SEM values from 6 rats.

Figure 3

Correlation between cocaine-induced increases in the K_m and psychomotor activation. Stereotypy was measured during the 1-min period prior to electrical stimulation using Waddington scale.