ABSTRACT
Synaptic dopamine (DA) is mainly regulated by the presynaptic DA transporter (DAT). Single-photon emission computerized tomography (SPECT) with the DAT radiotracer [¹²³I]FP-CIT assesses changes in synaptic DA availability when endogenous DA displaces [¹²³I]FP-CIT or competes for DAT. Here, we investigated the effects of haloperidol (HAL) and clozapine (CLZ) on [¹²³I]FP-CIT binding in the rat striatum and midbrain to assess the utility of [¹²³I]FP-CIT SPECT to quantify changes in synaptic DA availability. Rats underwent [¹²³I]FP-CIT SPECT after intraperitoneal administration of normal saline (vehicle), HAL (1 and 7 mg/kg), CLZ (10 and 54 mg/kg) and bupropion (BUP, a DAT blocker, 20 and 100 mg/kg). In the striatum and midbrain, percent differences in the nondisplaceable binding potential (BP(ND)) of [¹²³I]FP-CIT compared to the vehicle were calculated for the various drugs and doses. In another experiment, changes in endogenous striatal DA concentration were measured by in vivo microdialysis under the conditions used in the SPECT study. BUP dose-dependently occupied DAT at considerable levels. Compared to the vehicle, HAL decreased [¹²³I]FP-CIT BP(ND) in the striatum (−25.29% and −2.27% for 1 and 7 mg/kg, respectively) and to a greater degree in the midbrain (−58.74% and −49.64% for 1 and 7 mg/kg, respectively), whereas the CLZ-treated group showed a decrease in the midbrain (−38.60% and −40.38% for 10 and 54 mg/kg, respectively) but an increase in the striatum (18.85% and 38.64% for 10 and 54 mg/kg, respectively). Antipsychotic-induced changes in endogenous striatal DA concentrations varied across drugs and doses. The data demonstrate that [¹²³I]FP-CIT SPECT may be a useful preclinical technique for detecting increases in synaptic DA availability in the midbrain and striatum in response to HAL, with results comparable to those of in vivo microdialysis.
Subject(s)
Animals , Rats , Bupropion , Clozapine , Dopamine , Haloperidol , Mesencephalon , Microdialysis , Tomography, Emission-Computed, Single-PhotonABSTRACT
Acute traumatic spinal cord injury (SCI) represents one of the most devastating injuries that afflict the human body. Ascorbic acid ( AA) plays an important role in mammalian central nervous system, especially in SCI. In this study, the change of AA concentration after SCI was investigated by using an on-line electrochemical method integrated with in vivo microdialysis. A microdialysis probe (2 mm in length) was implanted into the spinal cord of an anesthetized rat (Thoracic-10). Microdialysis perfusate (2 μL/ min) was collected in the sample loop of an on-line injector for direct injection onto a glassy carbon electrode which was modified with the heat-treated single-walled carbon nanotubes (SWNTs). Normal ascorbic acid concentration in the extracellular fluids of spinal cords was (26. 17 ± 1. 25) μmol/ L (n =8). The experimental spinal cord injury, induced by a lesion at T-10, significantly increased the extracellular ascorbic acid levels to (53. 24± 1. 95) μmol/ L (n =8). This study provides the experimental evidence on the essential roles of ascorbic acid in spinal cord injuries.
ABSTRACT
OBJECTIVE: To determine the concentrations of evodiamine and rutacarpine in subcutaneous tissues of rats after administration of evodiae extract to evaluate the transdermal drug release properties. METHODS: The rats were treated with abdominal hair removal, followed by covering with black polyethylene film transdermal patch of evodiae extract. The concentrations of evodiamine and rutacarpine in the subcutaneous tissues at different time points were measured by microdialysis sampling technique combined with HPLC method. RESULTS: The maximum concentration(ρmax) of evodiamine in the dialysate was(417.24 ± 43.44) μg · mL-1, time to peak concentration (tmax) was (4.210 ± 0.630) h, and the area under the concentration time curve (AUC0→20) was (3 189.31 ± 789.97) μg · h · mL-1; the ρmax of rutacarpine was(287.13 ± 26.78) μg · mL-1, tmax was (3.980 ± 0.580) h, and the AUC0→16 was(l327.97 ± 245.87) μg · h · mL-1. CONCLUSION: In vivo microdialysis sampling technique combined with HPLC method can be used for the evaluation of transdermal drug release characteristics of evodiamine and rutacarpine. The method has the advantages of simple operation with high sensitivity and specificity. Evodiamine and rutacarpine in evodiae extract have the characteristics of slow transdermal penetration speed but high penetration amount.
ABSTRACT
Objective To investigate the effect of pre-ischemia physical activity on cognition and ascorbate content in medial prefrontal cortex (mPFC) after cerebral ischemia.Methods Twenty-four Sprague-Dowley rats were enrolled in this study and randomly divided into the following 4 groups:running-ischemia group,running group,ischemia group and shame operation group.Cerebral ischemia was brought about by permanent 2 vessels occlusion (2-VO) method.Treadmill running was used as physical activity training.Ascorbate in mPFC was monitored with in vivo microdialysis coupled with on-line electrochemical flow cell analysis.Passive avoidance was used to test cognitive function at 24 hours after 2-VO cerebral ischemia.Results Neurochemistry study showed that ascorbate level in mPFC increased within 3 hours after 2-VO ischemia and the increase was attenuated in the running-ischemia group.The baseline level of mPFC ascorbate in the four groups has no significant difference.Behavioral data indicated that 3 weeks pre-ischemia running promoted cognitive function recovery after 2-VO ischemia.Conclusion The pre-ischemia physical activity could increase the ascrobate storage in mPFC and enhance the antioxidant ability of this region.Therefore,it is one of the possible neurochemical mechanism underlying pre-ischemia physical activity for the improvement of cognitive function after cerebral ischemia.Thus pre-ischemia physical activity can be of benefit to cognition rehabilitation after stroke.