Limonene is a cyclic terpene found in citrus essential oils and inhibits methamphetamine-induced locomotor activity. Drug dependence is a severe neuropsychiatric condition that depends in part on changes in neurotransmission and neuroadaptation, induced by exposure to recreational drugs such as morphine and methamphetamine. In this study, we investigated the effects of limonene on the psychological dependence induced by drug abuse. The development of sensitization, dopamine receptor supersensitivity, and conditioned place preferences in rats was measured following administration of limonene (10 or 20 mg/kg) and methamphetamine (1 mg/kg) for 4 days. Limonene inhibits methamphetamine-induced sensitization to locomotor activity. Expression of dopamine receptor supersensitivity induced by apomorphine, a dopamine receptor agonist, was significantly reduced in limonene-pretreated rats. However, there was no significant difference in methamphetamine-induced conditioned place preferences between the limonene and control groups. These results suggest that limonene may ameliorate drug addiction-related behaviors by regulating postsynaptic dopamine receptor supersensitivity.
Animals ; Apomorphine ; Citrus ; Dopamine Agonists ; Dopamine ; Methamphetamine ; Morphine ; Motor Activity ; Oils, Volatile ; Rats ; Receptors, Dopamine ; Street Drugs ; Substance-Related Disorders ; Synaptic Transmission

Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson's disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks. Immunohistochemical analysis of tyrosine hydroxylase (TH) showed that EA treatment had no effect on TH expression in the ipsilateral striatum or substantia nigra pars compacta, though it alleviated several of the parkinsonian motor symptoms. Compared with the hemi-parkinsonian rats without EA treatment, the 100 Hz EA treatment significantly decreased apomorphine-induced rotation and increased the latency in the Rotarod test. Notably, the EA treatment reversed the 6-OHDA-induced down-regulation of VGluT1 in the STN. The results demonstrated that EA alleviated motor symptoms and up-regulated VGluT1 in the ipsilateral STN of hemi-parkinsonian rats, suggesting that up-regulation of VGluT1 in the STN may be related to the effects of EA on parkinsonian motor symptoms via restoration of function in the cortico-STN pathway.
Adrenergic Agents ; toxicity ; Animals ; Apomorphine ; pharmacology ; Disease Models, Animal ; Dopamine Agonists ; pharmacology ; Electroacupuncture ; methods ; Functional Laterality ; drug effects ; Male ; Medial Forebrain Bundle ; injuries ; Motor Activity ; drug effects ; physiology ; Neurons ; drug effects ; metabolism ; Oxidopamine ; toxicity ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus ; drug effects ; metabolism ; pathology ; Tyrosine 3-Monooxygenase ; metabolism ; Up-Regulation ; drug effects ; physiology ; Vesicular Glutamate Transport Protein 1 ; metabolism

OBJECTIVETo study the expression of nNOS and ultrastructural changes in the penile tissue of rats with prolactinoma-induced erectile dysfunction (ED).

METHODSWe established the model of prolactinoma in 20 male Westar rats by peritoneal injection of diethylstilbestrol (DES) and treated the control rats with normal saline (n = 10) or sterilized arachis oil (n = 10). After 8 weeks, we performed the apomorphine test and measured the weight of the pituitary gland and the levels of serum prolactin (PRL) and testosterone (T) to confirm the successful construction of the prolactinoma-induced ED model. Then we determined the expression of nNOS in the penile tissue by immunohistochemistry and examined the ultrastructural changes of the penile cavernosum under the transmission electron microscope.

RESULTSThe prolactinoma-induced ED model was successfully established in 15 rats. The weight of the pituitary gland was significantly increased in the rats treated with DES as compared with the normal saline and sterilized arachis oil controls ([46.7 ± 15.5] vs [11.7 ± 2.4] and [12.4 ± 2.3] mg, both P < 0.05). The level of serum PRL was markedly higher while that of T remarkably lower in the former than in the latter two groups ([1,744.9 ± 304.5] vs [11.5 ± 2.4] and [10.6 ± 1.9] ng/ml, both P < 0.0l; [1.54 ± 0.46] vs [3.11 ± 1.08] and [3.04 ± 1.11] ng/ml, both P < 0.05). The rate of penile erection was significantly reduced in the prolactinoma-induced ED model rats in comparison with the normal saline and arachis oil controls (16.7% vs 100% and 87.5%, both P < 0.05), and so was the expression of nNOS in the penile tissue (0.024 ± 0.011 vs 0.066 ± 0.019 and 0.058 ± 0.021, both P < 0.05). Transmission electron microscopy manifested significant ultrastructural changes in the endothelial and smooth muscle cells of the cavernous tissue in the prolactinoma-induced ED models.

CONCLUSIONThe ultrastructural changes of the penile cavernous tissue and the reduced expression of nNOS in penile tissue may be the most important mechanisms of prolactinoma-induced ED in rats.

Animals ; Apomorphine ; Carcinogens ; Diethylstilbestrol ; Erectile Dysfunction ; etiology ; Humans ; Male ; Myocytes, Smooth Muscle ; ultrastructure ; Nitric Oxide Synthase Type I ; metabolism ; Organ Size ; Penile Erection ; Penis ; enzymology ; ultrastructure ; Pituitary Neoplasms ; chemically induced ; complications ; Prolactin ; blood ; Prolactinoma ; chemically induced ; complications ; Rats ; Rats, Wistar ; Testosterone ; blood

OBJECTIVETo explore the expressions of HO-2 and CO in the corpus cavernosum of castrated rats in order to further study the pathogenesis of erectile dysfunction (ED).

METHODSWe randomly divided 72 male SD rats into four groups: normal control, sham operation, castration, and castration + ZnPP. We detected intracavernous pressure (ICP) and penile erection in the basic condition and after apomorphine (APO) induction, determined the expression of the HO-2 protein in the corpus cavernosum by laser scanning confocal microscopy, and measured the level of CO by spectrophotometry during different periods of penile erection.

RESULTSThe ICP in the basic condition and that after APO induction and the rate of penile erection were decreased significantly in the castration group ([11.68 ± 0.69] mmHg, [54.81 ± 3.86] mmHg, and 33.3%) and the castration + ZnPP group ([11.20 ± 0.71] mmHg, [41.17 ± 5.41] mmHg, and 22.2%) as compared with the normal control ([22.83 ± 2.66] mmHg, [66.92 ± 7.77] mm-Hg, and 100%) and the sham operation group ([23.35 ±2.22] mmHg, [70.43 ?7. 22] mmHg, and 100%) (all P <0. 01). After APO induction, ICP in the castration + ZnPP group was remarkably reduced in comparison with that in the castration group (P < 0.01), and so was the expression of the HO-2 protein before and during penile erection in the castration (445.4 ± 23.7 and 847.4 ± 35.0) and the castration + ZnPP group (390.1 ± 29.7 and 526.0 ± 52.5) compared with the normal control (512.7 ±57.4 and 1145.2 ± 89.8) and the sham operation group (583.7 ± 8.0 and 1016.3 ± 79.8), the expression of the HO-2 protein significantly decreased in the castration group (445.4 ± 23.7 and 847.4 ± 35.0) (P < 0.05 or 0.01), markedly lower in the castration + ZnPP than in the castration group during penile erection (P < 0.01) but with no significant differences among the four groups after it. Before, during and after penile erection, the levels of CO were remarkably decreased in the castration ([20.59 ± 1.01], [32.53 ± 1.26], and [18.71 ± 1.22] x 10(-7) nmol/L) and the castration +ZnPP group ([12.52 ± 1.05], [21.90 ± 1.02], and [16.56 ± 0.55] x 10(-7) nmol/L) as compared with the normal control ([26.76 ± 1.41], [48.25 ± 1.01], and [27.10 ± 1.58 ] x 10(-7) nmol/L) and the sham operation group ([25.41 ± 2.09], [ 47.90 ± 1.22], and [25.67 ± 1.20] x 10(-7) nmol/L) (P < 0.05 or 0.01), significantly lower in the castration + ZnPP than in the castration group during penile erection (P < 0.01).

CONCLUSIONDecreased expressions of HO-2 and CO may correlate with erectile dysfunction in castrated rats.

Animals ; Apomorphine ; pharmacology ; Carbon Monoxide ; metabolism ; Dopamine Agonists ; pharmacology ; Erectile Dysfunction ; etiology ; Humans ; Male ; Molecular Chaperones ; metabolism ; Orchiectomy ; Penile Erection ; drug effects ; Penis ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Functional dyspepsia (FD) is a prevalent idiopathic upper gastrointestinal (GI) disorder characterized by diverse symptomatology including epigastric pain or discomfort, postprandial fullness, and early satiety. Although its pathophysiological mechanisms have not yet been fully established, the available studies suggest that the etiology of FD is invariably multifactorial. Benachio-F(R) (BF) is a proprietary liquid formulation of 7 herbal extracts that has been proposed to address this multifactorial etiology using multi-drug phytotherapy. The pharmacological effects of BF, in comparison with those of two other herbal products (Whalmyungsu(R); WM and Iberogast(R); IB) were evaluated in rats. In a laparotomy-induced rat model of delayed GI transit, BF significantly accelerated the delayed gastric emptying caused by morphine, apomorphine, and cisplatin, and also significantly increased mean gastric transit, as compared to the control animals. BF markedly increased gastric accommodation in rats and produced higher gastric volume values than did the control treatment. The effects of BF were generally comparable or superior to those of WM and IB in these models. Furthermore, BF significantly stimulated biliary flow, as compared to the control treatment. These results indicated that BF might have great potential as an effective phytotherapeutic agent capable of reducing GI symptoms and increasing quality of life in FD patients.
Animals ; Apomorphine ; Cisplatin ; Dyspepsia ; Gastric Emptying ; Humans ; Models, Animal ; Morphine ; Phytotherapy ; Quality of Life ; Rats*

OBJECTIVETo investigate the effect of Bushengzhuyang Fang (Yangjing Capsule, YJC) on penile erectile function and its action mechanisms in rats.

METHODSFifty-six male SD rats were randomly divided into seven groups of equal number: blank control, daidzein, daidzein + testosterone, daidzein + sildenafil, daidzein + low-dose YJC, daidzein + medium-dose YJC, and daidzein + high-dose YJC. The rats in the blank control group were treated intragastrically with normal saline and those in the other groups with daidzein at the dose of 100 mg per kg per day for 30 days. Then the last five groups received additionally testosterone (4 mg per kg per day), sildenafil (2.5 mg per kg per day), low-dose YJC, (0.315 mg per kg per day), medium-dose YJC (0.63 mg per kg per day), and high-dose YJC (1. 26 mg per kg per day), respectively. At 0, 30 and 60 days of treatment, we observed the apomorphine-induced spontaneous erectile response and pathological changes in the corpus cavernosum of the rats, recorded the number of penile erection and erectile incubation period, and determined the serum levels of testosterone (T) and luteinizing hormone (LH).

RESULTSAt 30 days of treatment, the number of apomorphine-induced erections was decreased, the erectile incubation period prolonged, and the serum levels of T and LH reduced remarkably in all groups of rats (P < 0.05). Compared with the findings at 30 days, the number of penile erections was significantly decreased at 60 days in the daidzein group (1.39 ± 0.42 vs 2.67 ± 0.33, P < 0.05) and daidzein + low-dose YJC group (1.33 ± 0.49 vs 2.83 ± 0.61, P < 0.05); the erectile incubation period was markedly ex- tended ([16.33 ± 3.11] vs [8.50 ± 0.93] min and [15.50 ± 3.21] vs [8.63 ± 1.54] min, P < 0.05); and the serum levels of T ([5.34 ± 0.89] vs [1.24 ± 0.30] ng/ml and [5.28 ± 1.12] vs [2.07 ± 0.76] ng/ml, P < 0.05) and LH ([3.62 ± 0.37] vs [2.09 ± 0.12] ng/ml and [3.79 ± 0.28] vs [2.17 ± 0.33] ng/ml, P < 0.05) were significantly reduced in the daidzein and daidzein + low-dose YJC groups, respectively. Pathological examination revealed slightly decreased cavernous sinuses and blood vessels in the corpus cavernosum of the rats in the daidzein + testosterone, daidzein + sildenafil, daidzein + medium-dose YJC, and daidzein + high-dose YJC groups as compared with those in the blank control group.

CONCLUSIONHigh-dose Yangjing Capsule is efficacious for the recovery of erectile function in rats, especially for phytoestrogen-induced erectile dysfunction.

Animals ; Apomorphine ; pharmacology ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; chemically induced ; drug therapy ; Humans ; Isoflavones ; pharmacology ; Luteinizing Hormone ; Male ; Penile Erection ; drug effects ; physiology ; Penis ; drug effects ; pathology ; Phytoestrogens ; Phytotherapy ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate ; Sulfonamides ; therapeutic use ; Testosterone ; therapeutic use ; Vasodilator Agents ; therapeutic use

OBJECTIVETo discuss the protective effect of alkaloids from Piper longum (PLA) in rat dopaminergic neuron injury of 6-OHDA-induced Parkinson's disease and its possible mechanism.

METHODThe rat PD model was established by injecting 6-OHDA into the unilateral striatum with a brain solid positioner. The PD rats were divided into the PLA group (50 mg x kg(-1) x d(-1)), the madorpa group (50 mg x kg(-1) x d(-1)) and the model group, with 15 rats in each group. All of the rats were orally given drugs once a day for 6 weeks. Meanwhile, other 15 rats were randomly selected as the sham operation group, and only injected with normal saline in the unilateral striatum. The behavioral changes were observed with the apomorphine (APO)-induced rotation and rotary rod tests. The number of tyrosine hydroxylase (TH)-positive cells in rat substantia nigra and the density of TH-positive fibers in striatum were detected by tyrosine hydroxylase immunohistochemistry. The content of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS) in rat substantia nigra and striatum were measured by the spectrophotometric method.

RESULTAfter being induced by APO, PD rats showed obvious rotation behaviors, with decreased time stay on rotary rod and significant reduction in the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. The activities of SOD, GSH-Px, CAT, the content of GSH and the total antioxidant capacity significantly decreased, whereas the activities of NOS and the content of MDA, NO significantly increased. PLA could significantly improve the behavioral abnormality of PD rats and increase the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. It could up-regulate the activities of SOD, GSH-Px, CAT, the content of GSH and the total antioxidant capacity, and decrease the content of NOS and the content of MDA, NO.

CONCLUSIONAlkaloids from P. longum shows the protective effect in substantia nigra cells of 6-OHDA-induced PD model rats. Its mechanism may be related with their antioxidant activity.

Administration, Oral ; Alkaloids ; administration & dosage ; pharmacology ; Animals ; Apomorphine ; pharmacology ; Catalase ; metabolism ; Dopamine Agonists ; pharmacology ; Dopaminergic Neurons ; drug effects ; metabolism ; pathology ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Motor Activity ; drug effects ; Neostriatum ; drug effects ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Oxidopamine ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; prevention & control ; Piper ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; metabolism ; Superoxide Dismutase ; metabolism ; Tyrosine 3-Monooxygenase ; metabolism

A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.
Animals ; Apomorphine/pharmacology ; Behavior, Animal/drug effects ; Corpus Striatum/drug effects/pathology ; Disease Models, Animal ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Glucose/metabolism ; Injections, Intraperitoneal ; Levodopa/pharmacology ; Male ; Medial Forebrain Bundle/drug effects/pathology ; Oxidopamine/*toxicity ; Parkinson Disease/metabolism/pathology ; Positron-Emission Tomography ; Quinolinic Acid/*toxicity ; Rats ; Rats, Wistar ; Striatonigral Degeneration/*chemically induced/metabolism/pathology ; Touch/drug effects

OBJECTIVETo research the mechanism of dopamine (DA) controlled memory in mice.

METHODSMice received i.p. injection of scopolamine (0.3 mg/kg, SCOP 0.3, and 3.0mg/kg, SCOP 3.0, respectively, n = 10) and saline (NS, n = 10) for 60 days in experiment 1. Memory of mice was detected by dark avoidance behavior in the 53" d and the 60"' d. Animals were sacrificed after the memory test; brain tissues were processed for Fos-ir and TH-ir by immunohistochemistry. Mice were divided into four groups according results of expri-ment 1, they received i.p. injection of apomorphine (0.1 mg/kg, APO 0.1, 0.5 mg/kg, APO 0.5, and 2.0 mg/kg, APO2.0 respectively, n = 10).

RESULTSMemory was inhibited in mice injected scopolamine 3.0 mg/kg. Latency was significantly less than in NS group, only 1/ 4 that of NS group (P > 0.05). The number of mistake of SCOP 3.0 group increased about four times than that of NS group (P > 0.05). But there was no difference of latency and number of mistake between SCOP 0.3 and NS group in expriment 1. Scopolamine-induced memory deficit was associated with decreased cellular activation, indicated by Fos immunoreactive (ir) staining, in NAcc CA1 and CA3 (P < 0.05), and also associated with decreases in the number of cells labeled for tyrosine hydroxylase (TH-ir), the rate limiting enzyme for dopamine conversion (P < 0.01) and the number of cells co-labeled for TH-ir/Fos-ir (P <0.01) in the ventral tegmental area(VTA), apomorphine lessened scopolamine-induced memory deficit in experiment 2. The number of cells co-labeled for TH-ir/Fos-ir (P <, 0.05) was increased in VTA after apomorphine treatment.

CONCLUSIONApomorphine lessened scopolamine-induced memory deficit in mice by increasing DA activities in VTA.

Animals ; Apomorphine ; pharmacology ; Disease Models, Animal ; Dopamine Agonists ; pharmacology ; Male ; Memory Disorders ; chemically induced ; drug therapy ; Mice ; Scopolamine Hydrobromide ; toxicity

OBJECTIVETo investigate the clinical effect of Compound Xuanju Capsule combined with apomorphine hydrochloride on penile erectile dysfunction (ED).

METHODSWe treated 115 ED patients with Compound Xuanju Capsule plus apomorphine hydrochlorid (trial group), and another 111 with apomorphine hydrochloride alone (control group), both for two months. Then we compared the IIEF-5 scores between the two groups.

RESULTSAfter treatment, the IIEF-5 scores were 17.85 +/- 2.68 and 13.96 +/- 3.25 in the trial and control group, respectively, significantly higher than 11.42 +/- 2.68 and 13.96 +/- 3.25 before treatment (P < 0.01). There were statistically significant differences between the two groups either in post-treatment IIEF-5 scores (P < 0.01) or in the rates of obvious effectiveness, effectiveness and total effectiveness.

CONCLUSIONCompound Xuanju Capsule combined with apomorphine hydrochloride has a good curative effect on ED, and deserves general clinical application.

Adult ; Aged ; Apomorphine ; therapeutic use ; Capsules ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Middle Aged ; Phytotherapy ; Treatment Outcome ; Young Adult