Response by the neurotensin systems of the basal ganglia to cocaine treatment

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Abstract

Multiple administrations of high doses of cocaine had profound effects on the neurotensin (NT) systems of the basal ganglia. Approximately 200–300% increases in striatal content of neurotensin-like immunoreactivity (NTLI) were observed 1–8 h following five doses of 30 mg/kg per dose of cocaine. The effect subsided by 48 h after treatment. Significant changes in striatal NTLI levels were not observed after a single dose of this stimulant. The nigral NT systems appeared to be even more sensitive to cocaine administration. Compared to striatal changes, increases in nigral NTLI content were greater (as much as 455% of control), required lower cocaine doses (20 mg/kg per dose), lasted longer (still elevated to 200% of control after 48 h) and were significant following a single cocaine exposure. The response of the striatal NT systems to cocaine appeared to be mediated principally by dopamine D-1 receptors, while both D-1 and D-2 receptors contributed to the response by the nigral NT projections. Specific dopamine, but not serotonin, uptake blockers caused increases in striatal and nigral NTLI concentrations similar to that seen with cocaine treatments, suggesting that interference with the dopamine uptake carrier complex by cocaine was responsible for its actions on extrapyramidal NT systems.

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    Similar results have been found in the mPFC where cocaine pretreatment induces an increase in NT immunoreactivity in rats, and where activation of NT receptors stimulates firing of DA neurons (Rompré et al., 1998; Alburges and Hanson, 1999). Additional evidence of a link between NT and cocaine is provided by studies showing an increase in NT in the striatum, substantia nigra, NAc, and frontal cortex after cocaine exposure, apparently due to the failure of the DA reuptake mechanism (Cain et al., 1993; Hanson et al., 1989), while at the same time cocaine causes a decrease in NT binding in the VTA and PFC (Pilotte et al., 1991). Taken together, these findings suggest that NT is involved in mediating the rewarding properties of psychostimulants such as cocaine.

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