Abstract
Administration of cocaine induces long-term behavioral and biochemical effects. Neurochemical changes involve mechanisms of post-receptor signal transduction and gene expression (Nestler, E.J., J Neurosci 12: 2439,1992). In the present study we sought to determine whether single or repeated treatment with or withdrawal from cocaine (15 mg/kg, i.p.) modify rates of local cerebral protein synthesis (1CPSleu) as measured with the [1-14C]leucine method (Smith et al., PNAS 85:9341, 1988) in the adult, male, Sprague Dawley rat. Three sets of paired experiments were carried out and results were analyzed by statistical methods for paired data. In the first set, eight pairs of rats were treated with normal saline, i.p., for seven days and either normal saline or cocaine on the eighth day, 30 min prior to the initiation of the measurement of 1CPSleu with a bolus injection of [14C]leucine. In this set 1CPSleu was reduced by about 10% throughout the brain in the cocaine-treated rats; reductions were highly statistically significant in the shell of the nucleus accumbens (P=0.0003) and in some other limbic areas (P≤0.007). The second set of seven pairs was similar to the first except that rats received cocaine for seven days and either normal saline or cocaine on the eighth day. There were no statistically significant differences in 1CPSleu found in these pairs. In the third set, eight pairs of rats were injected with either normal saline or cocaine for eight days and determinations of 1CPSleu were carried out on the 15th day. The results of these delayed experiments showed increases of about 10% in 1CPSleu in selective brain regions, i.e., prefrontal and primary olfactory cortex (P≤0.006), hippocampus, and thalamic nuclei (P≤0.05). Nucleus accumbens and septal nuclei were not affected. Our results suggest that acute cocaine treatment and withdrawal from chronic cocaine treatment both alter rates of protein synthesis in distinctly different ways and in different brain regions.
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Orzi, F., Sun, Y., Pettigrew, K. et al. Cocaine Alters Rates of Regional Protein Synthesis in the Rat Brain. Neuropsychopharmacol 11, 279 (1994). https://doi.org/10.1038/sj.npp.1380188
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DOI: https://doi.org/10.1038/sj.npp.1380188