A solid lipid particle formulation of long pepper extract reduces pain and astrocyte activation in a rat model of neuropathic pain.

OBJECTIVES: To investigate the effects of solid lipid microparticle (SLM) creams containing a long pepper extract (LPE) or piperine on neuropathy-related pain and the expression of glial fibrillary acidic protein (GFAP) as a measure of astrogliosis. METHODS: Neuropathic pain in male Spraque Dawley rats was induced by sciatic nerve ligation (SNL) and followed by treatment with LPE-SLM, piperine-SLM, capsaicin or vehicle creams. The pain score was assessed by thermal hyperalgesia test. The GFAP expression in the spinal cord was determined by immunohistochemistry. RESULTS: Pain scores were significantly increased after SNL and decreased when treated by LPE-SLM. The number of GFAP immunopositive cells was significantly increased in the SNL rats. Treated by LPE-SLM and capsaicin creams resulted in a significant reduction of the number of GFAP immunopositive cells. The LPE-SLM treated rats showed greater effects than the piperine and capsaicin preparations. CONCLUSIONS: The LPE-SLM cream has a potential effect on pain attenuation via a decrease of spinal astrocyte activation-related mechanism. The LPE in SLM preparation could provide an alternative therapeutic strategy for treating neuropathic pain.

Effect of Methamphetamine Exposure on Expression of Calcium Binding Proteins in Rat Frontal Cortex and Hippocampus.

Methamphetamine (METH) is a psychostimulant drug with potent effects on the central nervous system that can cause psychotic symptoms similar to those of schizophrenia. Specific alterations in GABAergic neuronal markers have been reported in schizophrenia and animal models of psychotic illness. The aim of this study was to determine whether there are changes in subpopulations of GABAergic neurons, defined by the presence of calcium binding proteins (CBPs), in animal models of METH abuse. Rats received acute (Binge) doses of 4 × 6 mg/kg, a chronic escalating dose regime (0.1-4 mg/kg over 14 days) or a combination of the two and were compared with a vehicle-administered control group. Brains were taken and sections of frontal cortex (Cg1) and hippocampus (dentate gyrus and CA1-3 regions) underwent immunostaining for three CBPs [parvalbumin (PV), calbindin (CB), and calretinin (CR)]. Significant decreases in PV-immunoreactive (IR) neurons in each METH group and all regions were observed. Smaller METH-induced deficits in CB-IR cells were observed, reaching significance primarily following chronic METH regimes, while CR-IR was significantly reduced only in frontal cortex following chronic administration. These results suggest that METH regimes in rats can induce selective deficits in GABAergic neuronal subtypes similar to those seen in schizophrenia and may underlie the psychosis and/or cognitive impairment that can occur in METH abuse and dependence.

Changes in the neuronal glutamate transporter EAAT3 in rat brain after exposure to methamphetamine.

Methamphetamine (METH), an addictive psychostimulant, can induce glutamate release in several brain areas such as cerebral cortex, hippocampus and striatum. Excess glutamate is ordinarily removed from the synaptic cleft by glutamate transporters for maintaining homoeostasis. EAAT3, a subtype of glutamate transporter expressed mainly by neurons, is a major glutamate transporter in the hippocampus and cortex. Therefore, this study examined the effects of acute and sub-acute METH administration on the expression of the EAAT3 in the hippocampal formation, striatum and frontal cortex. Male Sprague-Dawley rats received vehicle injections (i.p.) for 13 days followed by one injection of METH (8 mg/kg, i.p.) on day 14 in acute group. Animals received METH (4 mg/kg, i.p.) or vehicle for 14 days in sub-acute and control groups, respectively. EAAT3 immunoreactivity was determined by western blotting followed by measurement of the integrated optical density. A significant increase in EAAT3 was found in the hippocampal formation after sub-acute, but not acute, METH administration. Conversely, a significant decrease in EAAT3 in striatum was observed in both acute and sub-acute groups. A trend towards a decrease in EAAT3 was also found in frontal cortex in the sub-acute group. Our results of decreased EAAT3 in striatum and frontal cortex suggest deficits of cortico-striatal glutamatergic synapses after METH exposure. Increased EAAT3 expression in the hippocampus may be a compensatory response to possible deficits of glutamatergic neurotransmission induced by METH. Moreover, our findings provide further support for glutamatergic dysfunction with abnormalities involving a transporter important in the regulation of neuronal glutamate.