Methamphetamine has been reported to be an important drug in the field of reproductive toxicology. The aim of this study was to investigate the effects of methamphetamine administrations on sperm morphology, sperm concentration and apoptotic activity inside seminiferous tubule in male rats. Rats were administered a dose of 8 mg kg(-1) , intraperitoneally (IP), for acute group and a dose of 4 mg kg(-1) , IP, once daily for 14 days for sub-acute group. Percentage of normal sperm morphology was decreased in acute group when compared with control. Total numbers of sperm count were significantly decreased in acute and sub-acute groups. Apoptotic activities were most abundant in the seminiferous tubules of acute treated animals with a highly significant increase in the number of apoptotic cells per tubule. Those effects of methamphetamine seem to be dose-dependent. The results suggest that methamphetamine not only works as drug of abuse in central nervous system, but also in gametogenesis of males.
Methamphetamine (METH) is known to damage neurons and induce psychosis. It can also induce apoptosis in seminiferous tubules and affect sperm quality. The present study was carried out to investigate the effect of a rat model of METH addiction on sperm quality and expression of progesterone receptors (PR) and estrogen receptors (ER) in the testis. Sperm quality parameters including sperm motility, sperm morphology and sperm concentration were examined. Protein and gene expressions PR, ERα and ERβ were studied using immunohistochemistry and reverse transcriptase-polymerase chain reaction, respectively. The percentages of normal sperm motility and normal sperm morphology were significantly decreased in animals receiving METH, especially in escalating dose (ED METH) and escalating dose-binge (ED-binge METH) groups when compared with control. In addition, sperm concentrations in ED METH and ED-binge METH groups were numerically decreased. PR, ERα and ERβ immunoreactive cells were significantly decreased in spermatogonia, spermatogenic cells and especially in Sertoli cells in all METH-treated groups. Furthermore, messenger RNA expression of PR, ERα and ERβ were also significantly decreased in all METH-treated animals. These results indicate that METH can induce abnormal sperm quality. These changes of sperm quality may relate to the reduction of PR, ERα and ERβ expressions in male germ cells and Sertoli cells which are essential for spermatogenesis and development of sperm.
Gamma-aminobutyric acid (GABA), GABA-A receptors and GABA transporter 1 (GAT1) were reported to be involved in the proliferation of Leydig cells, testosterone production and spermatogenesis. Since methamphetamine (METH) has been reported to have adverse effects on testis and its functions, the aim of this study was therefore to determine the changes of GABAergic activity in testis after METH exposure. Male Sprague-Dawley rats were divided into control, acute binge (AB-METH), escalating dose (ED METH) and escalating dose-binge (ED-binge METH) groups. After sacrifice, rat testes were removed and used to estimate GABA concentration and the expression of GABA-A receptor, GAD1, GAD2 and GAT1 genes by using HPLC and RT-PCR, respectively. The GABA concentration was significantly increased in all METH-administrated groups. In addition, significant increases of GABA-A α1 receptor and GAD1 genes expression were found in the ED-binge METH group. Gene expressions of GAT1 were numerically decreased in all METH-administrated rats and reached significant in the ED METH group. These results indicated a compensatory upregulation of GABA production and its functions in testis after METH exposure. Thus, these changes might represent a homeostatic response of GABAergic to the adverse effects of METH.
The present findings indicate that rs6265 is associated with METH dependence in the Thai population, with the GG genotype greater in METH-dependent subjects but reducing the emergence of METH-dependent psychosis.
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.
Depression and antidepressant drugs induce adverse effects in male reproduction. Therefore, it is important to investigate alternative treatment for depression without adverse effects on the male reproductive system. The aim of this study was to determine the effect of pre-germinated brown rice (PGBR) on sperm quality, testicular structure and androgen receptor (AR) expression in rat model of depression. Male Sprague Dawley rats were divided into five groups including control (distilled water only), depression induced by forced swimming test (FST), FST + fluoxetine (antidepressant drug), FST + GABA (gamma-aminobutyric acid) (standard) and FST + PGBR. When compared with the control, sperm motility showed a significant decrease in FST + fluoxetine group. Sperm morphology also decreased significantly in depression and FST + fluoxetine groups. The morphological changes of seminiferous tubules showed significant increases in depression and FST + fluoxetine groups, while AR expression showed significant decreases in depression, FST + fluoxetine and FST + GABA groups. Interestingly, there were no significant differences in all sperm quality parameters, testicular structure and AR expression in FST + PGBR group. These findings reflect the recovery effects of PGBR treatment on sperm quality, morphological changes of seminiferous tubules and AR expression in stress-induced rats. Therefore, PGBR may potentially develop for the treatment for depression without adverse effect on male reproduction.
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