Brain regional changes of guanine nucleotide binding protein-inhabitant 2 in acute and chronic morphine-tolerant and -dependent rats

BACKGROUND: Drug addiction involves two main central nervous systems, namely the dopamine and noradrenaline systems. These systems are primarily distributed in five brain regions: the ventral tegmental area. the nucleus accumbens, the prefrontal cortex, the hippocampus, and the locus coeruleus. OBJECTIVE: To investigate regional changes of guanine nucleotide binding protein-inhabitant 2 (Gi2) in dopaminergic and noradrenergic neurons in brains of morphine-tolerant and -dependent rats. DESIGN, TIME, AND SETTING: A randomized control study was performed at the Department of Neurobiology in the Second Military Medical University of Chinese PLA (Shanghai, China) between September 2002 and March 2004. MATERIALS: Thirty-six, healthy, male, Sprague-Dawley (SD) rats were used to establish morphine-dependent models. Morphine hydrochloride was a product of Shenyang First Pharmaceutical Factory (China): naloxone hydrochloride was a product of Beijing Four-Ring Pharmaceutical Factory (China): and a subunit of G(i2) antibody was offered by Santa Cruz Biotechnology, [tic (USA). METHODS: Thirty-six SD rats were randomly divided into six groups (n = 6): (1) acute morphine-dependent group, (2) acute abstinent group, (3) acute control group, (4) chronic morphine-dependent group, (5) chronic abstinent group, and (6) chronic control group. Rats in the acute morphine-dependent and the acute groups were injected with morphine 5 mg/kg), one injection every two hours, for a total of eight injections. In the acute and chronic morphine-dependent rat models, morphine withdrawal syndrome was precipitated by an injection of naloxone (5 mg/kg). Rats in the acute control group were given a peritoneal injection of physiological saline at the same administration time as the above two groups. Rats in the chronic morphine-dependent and chronic abstinent groups were injected with morphine three times per day. The administration dose on day 1 was initially 5 mg/k,, at 20:00, which increased by 5 mg/kg at 8:00, 12:00. and 20:00 until day 7. On day 13, the close Continuously increased by 10 mg/kg until a chronic morphine-dependent rat model Wits successfully induced. Afterwards, the rats presented with withdrawal syndrome on naloxone (5 mg/kg) at 8:00 on the same day. Rats in the chronic control group were injected with physiological saline at the same time of the two chronic groups. MAIN OUTCOME MEASURES: The concentration of G(i2) protein in the five brain regions (ventral tegmental area, nucleus accumbens, prefrontal cortex, locus coeruleus, and hippocampus) wits detected by immunohistochemistry. RESULTS: In the acute morphine-dependent and acute abstinent groups, G(i2) Protein concentration was significantly, decreased in the nucleus accumbens, compared to the acute control group (P < 0.01), while no obvious changes were detected in other brain regions.. In the chronic morphine-dependent and chronic abstinent groups, G(i2) protein concentration was significantly decreased in the nucleus accumbens, but significantly increased in the locus coeruleus (P < 0.01) compared to the chronic control group. CONCLUSION: Morphine dependence and tolerance may induce obvious reductions of G(i2) protein levels in the nucleus accumbens of rats. Chronic morphine dependence desensitizes the homologous neurons.