RESUMO
Methamphetamine (METH) markedly increases dopamine (DA) release in the mesolimbic DA system, which plays an important role in mediating the reinforcing effects of METH. METH-induced DA release results in the formation of reactive oxygen species (ROS), leading to oxidative damage. We have recently reported that ROS are implicated in behavior changes and DA release in the nucleus accumbens (NAc) following cocaine administration. The aim of this study was to evaluate the involvement of ROS in METH-induced locomotor activity, self-administration and enhancement of DA release in the NAc. Systemic administration of a non-specific ROS scavenger, N-tert-butyl-α-phenylnitrone (PBN; 0, 50 and 75 mg/kg, IP) or a superoxide-selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL; 0, 50 and 100 mg/kg, IP), attenuated METH-induced locomotor activity without affecting generalized behavior in METH-naïve rats. PBN and TEMPOL significantly attenuated METH self-administration without affecting food intake. Increased oxidative stress was found in neurons, but not astrocytes, microglia or oligodendrocytes, in the NAc of METH self-administering rats. In addition, TEMPOL significantly decreased METH enhancement of DA release in the NAc. Taken together, these results suggest that enhancement of ROS in the NAc contributes to the reinforcing effect of METH.
Assuntos
Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Dopamina/metabolismo , Locomoção/efeitos dos fármacos , Metanfetamina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Antioxidantes/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Óxidos N-Cíclicos/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Núcleo Accumbens/metabolismo , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Autoadministração , Marcadores de SpinRESUMO
BACKGROUND: Most ETOH addiction preclinical studies have focused on the rewards of chronic ETOH self-administration or the ETOH reinstatement model. Acute ETOH administration studies are scarce despite the potential of ETOH to cause sedation, intoxication and reduced acute functional tolerance. Here, we established a rat model of acute ETOH administration induced by an intraperitoneal injection of 1 g/kg ethanol and assessed the similarities in physiological and behavioral effects between acupuncture and Sigma1 R antagonists. METHODS: Male Wistar rats (300-330 g) received pretreatment with (1) saline injection, (2) saline + mechanical stimulation using a mechanical acupuncture instrument (MAI) for acupuncture at the Shenmen (HT7), (3) ETOH (1 g/kg) injection, (4) ETOH + HT7, or (5) the selective σ1 R antagonist BD 1047 (3, 10, or 30 mg/kg, intraperitoneal (IP) injection). ETOH (1 g/kg) or saline was IP injected after 10 min. Then, ETOH-induced immobility was evaluated in an open field arena, ultrasonic vocalizations (USVs) indicating ethanol-induced emotional changes were recorded in a recording chamber, and the rats were sacrificed for the analysis of protein levels of σ1 R in several regions of the brain. RESULTS: Acute ethanol exposure increased the immobile time, 22-kHz USVs, and protein levels of σ1 R in the ventral tegmental area (VTA). However, pretreatment with acupuncture at HT7 induced recovery of immobile time, reduced 22-kHz USVs, and regulated the protein levels of σ1 R in the VTA. These effects have similarities with IP injection of BD 1047 (10 mg/kg). CONCLUSION: This study showed that acupuncture at HT7 regulates immobility and 22-kHz USVs via Sigma1 R in the VTA upon acute ETOH exposure.
RESUMO
BACKGROUND: Acupuncture has become a common complementary and alternative treatment approach for anxiety and depression. However, there is little research on the detailed mechanism of acupuncture therapy relieving depression. Previously, 17ß-estradiol (E2) was shown to prevent oxidative stress and endoplasmic reticulum (ER) stress in ovariectomized (OVX) rats. This study investigated whether stimulation of Sanyinjiao (SP6) using a mechanical acupuncture instrument can alleviate depression-like behavior caused by estrogen deficiency in OVX rats. Furthermore, we found that acupuncture reduced ER stress and oxidative stress-related proteins expression. METHODS: The OVX operation was performed on female SD rats that were separated into four groups: The E2 (2.5 µg/kg, i.p.) injection group (OVX + E2), the OVX group (OVX), and the OVX with acupuncture stimulation group (OVX + SP6). Non-acupoint stimulation group (OVX + NonAcu). The acupuncture point stimulation began three weeks after surgery. The depressive behavior was analyzed by the forced swim test and open field test. The 8-OHDG, BiP, Sigma receptor 1, pJNK, PDI, Ero1-Iα and Calnexin protein levels were evaluated by immunoreactivity in the amygdala. RESULTS: Acupuncture stimulation reduced depressive behavior and altered depression-related proteins. Stimulation of SP6 decreased the immobility time of the FST and altered the ER stress and oxidative stress marker proteins, such as 8-OHDG, BiP, pJNK, PDI, Ero1-Ia and Calnexin. CONCLUSION: Our results indicated that acupuncture at SP6 showed a significant antidepressant-like effect on an OVX-induced depression rat model by mitigation of ER stress and oxidative stress in amygdala.
RESUMO
Menopause-related depression devastates women's quality of life after middle age. Previous research has shown that estrogen hormone therapy has serious adverse effects; thus, complementary and integrative therapies have been considered clinically. The present study investigates whether stimulation of an acupoint using a mechanical acupuncture instrument (MAI) can mitigate depression-like behavior caused by estrogen deficiency in ovariectomized (OVX) rats. The animals were divided into Sham OVX, OVX, OVX + Sameumgyo (SP6) and OVX + NonAcu (non-acupuncture point) groups. MAI stimulation significantly increased the total distance traveled in the open-field test and the number of open-arm entries in the elevated plus maze and decreased the duration of immobility in the forced swim test. In addition to this decrease in depression-like behavior, brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) release increased in the hippocampus in response to MAI treatment, but estradiol levels did not recover. Furthermore, microinjection of the BDNF receptor antagonist ANA-12 (0.1 pmol/1 µl) into the hippocampus before MAI stimulation significantly suppressed the recovery of NPY levels. Taken together, these findings indicate that MAI stimulation at SP6 facilitates an estradiol-independent BDNF-NPY cascade, which may contribute to its antidepressant effects in OVX rats, an animal model of menopausal disorders.
Assuntos
Pontos de Acupuntura , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/terapia , Menopausa/psicologia , Neuropeptídeo Y/metabolismo , Animais , Depressão/etiologia , Depressão/metabolismo , Depressão/psicologia , Modelos Animais de Doenças , Estradiol/metabolismo , Feminino , Hipocampo/metabolismo , Humanos , Menopausa/metabolismo , Ovariectomia/efeitos adversos , Ratos , Resultado do TratamentoRESUMO
Spinal cord injury (SCI) frequently results in chronic neuropathic pain (CNP). However, the understanding of brain neural circuits in CNP modulation is unclear. The present study examined the changes of ventral tegmental area (VTA) putative GABAergic and dopaminergic neuronal activity with CNP attenuation in rats. SCI was established by T10 clip compression injury (35 g, 1 min) in rats, and neuropathic pain behaviors, in vivo extracellular single-cell recording of putative VTA gamma-aminobutyric acid (GABA)/dopamine neurons, extracellular GABA level, glutamic acid decarboxylase (GAD), and vesicular GABA transporters (VGATs) were measured in the VTA, respectively. The results revealed that extracellular GABA level was significantly increased in the CNP group (50.5 ± 18.9 nM) compared to the sham control group (10.2 ± 1.7 nM). In addition, expression of GAD65/67, c-Fos, and VGAT exhibited significant increases in the SCI groups compared to the sham control group. With regard to neuropathic pain behaviors, spontaneous pain measured by ultrasound vocalizations (USVs) and evoked pain measured by paw withdrawal thresholds showed significant alteration, which was reversed by intravenous (i.v.) administration of morphine (0.5-5.0 mg/kg). With regard to in vivo electrophysiology, VTA putative GABAergic neuronal activity (13.6 ± 1.7 spikes/sec) and putative dopaminergic neuronal activity (2.4 ± 0.8 spikes/sec) were increased and decreased, respectively, in the SCI group compared to the sham control group. These neuronal activities were reversed by i.v. administration of morphine. The present study suggests that chronic increase of GABAergic neuronal activity suppresses dopaminergic neuronal activity in the VTA and is responsible for negative emotion and motivation for attenuation of SCI-induced CNP.