Ethanol lowers methamphetamine's excitatory effects on locomotion and neuronal activity through mGluR2/3

• Main Authors: Kee-Deng Jou, 周可登
• Other Authors: 袁宗凡
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/14669572525196663949

碩士 === 慈濟大學 === 生理暨解剖醫學碩士班 === 104 === Results from epidemiological studies indicate that addicts usually use several drugs in combination. For example, several researchers have reported that novice and experienced illicit methamphetamine (MA) users frequently use the stimulant in combination with alcohol (EtOH). MA combined with EtOH increased heart rate and euphoria more than either drug alone and attenuated alcohol-related subjective feelings of intoxication. This drug combination, however, may have dangerous consequences. Many studies of its toxic functions of single drug have been done on animals and humans, but the mechanism of drug combination is still poorly understood. Previous behavioral studies indicated that EtOH might synergistically alter the acts of MA, including locomotion in ratswith high alcohol preference. The effects on locomotion and mechanism in SD rats, however, are not yet clear. Nucleus accumbens (NA) and motor cortex are the nuclei involving in the behavioral effects of MA or EtOH. It becomes an acceptable possibility that NA or motor cortex may be the loci where EtOH and MA interact with each other and then modulate MA-induced hyperlocomotion. Previously, it was reported that selective blockade of group II metabotropic glutamate receptors (mGluR2/3) in the NA produces hyperlocomotion in rats previously exposed to amphetamine.The aim of the study is to investigate if the mGlu2/3R may involve in that EtOH modulates MA-induced locomotion and neuronal activities. In the first experiment, drugs were administered systemically (saline, MA 2 mg/kg, EtOH 1.6 g/kg or MA with EtOH, i.p.). We found that EtOH could lower MA-induced hyperlocomotion and the number of cFos-immunoreactive (-ir) cells in primary motor cortex (M1) and NA. In the second experiment, different rats were tested following microinjections into the lateral ventricle (LV) (saline or LY341495 4μg/3μl), than injection systemically (saline, MA 2 mg/kg, EtOH 1.6 g/kg or MA with EtOH,i.p.). In the third experiment, different rats received LV injection (saline or LY354740 3 μg/3μl)followed by injection of MA (2 mg/kg, i.p.). We found that LY341495 may reverse the inhibitory effects of EtOH on MA-induced hyperlocomotion and the number of cFos-ir cells in M1, secondary motor cortex (M2) and NA shell. LY354740 lowers the MA’s stimulatory effects on locomotion and number of cFos-ir cells in motor cortex and NA. The results indicated that mGluR2/3, particularly those found in M1 and NA shell, may be well positioned to involve in the action that EtOH modulates MA-induced locomotion and neuronal activation.