Locomotor Activity Of Animals Research Articles

Role of hippocampal dopamine receptors in the antinociceptive responses induced by chemical stimulation of the lateral hypothalamus in animal model of acute pain

Dopamine is the predominant catecholamine neurotransmitter in the mammalian brain which has been shown to play a critical role in antinociceptive process. Previous studies have shown that the role of CA1 region of the hippocampus in antinociception induced by stimulation of the lateral hypothalamus (LH) through the dopaminergic system in tonic pain. In this study, we tried to assess the involvement of intra-hippocampal D1- and D2-like dopamine receptors in the LH stimulation-induced antinociception during the tail-flick test as an animal model of acute pain. Ninety-five male Wistar rats were unilaterally implanted with two separate cannulae into the LH and CA1. Animals received intra-CA1 infusion of SCH-23390 (0.25, 1 and 4 µg/rat), as a D1-like dopamine receptor antagonist and sulpiride (0.125, 0.25, 1 and 4 µg/rat), as a D2-like dopamine receptor antagonist, 2 min before intra-LH administration of carbachol (250 nM/rat). The antinociceptive effects of SCH-23390 and sulpiride were measured by using a tail-flick analgesiometer and represented as the maximal possible effect (%MPE). Also, the locomotion tracking apparatus was used to measure the locomotor activity of animals. Results showed that intra-CA1 administration of SCH-23390 or sulpiride could prevent the intra-LH carbachol-induced antinociception. This effect was a little more dominant after blocking the D2-like dopamine receptor in the CA1. These findings revealed that D1- and D2-like dopamine receptors within the CA1 play an important role in antinociceptive responses induced by chemical stimulation of the LH. It could be suggested that dopamine receptors in the CA1 were triggered by LH orexinergic projections.

Snake C-Type Lectins Potentially Contribute to the Prey Immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri Venoms.

Snake venoms contain components selected to immobilize prey. The venoms from Elapidae mainly contain neurotoxins, which are critical for rapid prey paralysis, while the venoms from Viperidae and Colubridae may contain fewer neurotoxins but are likely to induce circulatory disorders. Here, we show that the venoms from Protobothrops mucrosquamatus and Trimeresurus stejnegeri are comparable to those of Naja atra in prey immobilization. Further studies indicate that snake C-type lectin-like proteins (snaclecs), which are one of the main nonenzymatic components in viper venoms, are responsible for rapid prey immobilization. Snaclecs (mucetin and stejnulxin) from the venoms of P. mucrosquamatus and T. stejnegeri induce the aggregation of both mammalian platelets and avian thrombocytes, leading to acute cerebral ischemia, and reduced animal locomotor activity and exploration in the open field test. Viper venoms in the absence of snaclecs fail to aggregate platelets and thrombocytes, and thus show an attenuated ability to cause cerebral ischemia and immobilization of their prey. This work provides novel insights into the prey immobilization mechanism of Viperidae snakes and the understanding of viper envenomation-induced cerebral infarction.

Influência da Ayahuasca na Resolução de Problemas com Ratos Wistar

A resolução de problemas por uma nova cadeia de respostas ocorre quando, diante de uma situação problema, é emitida uma nova resposta resultante do encadeamento de duas ou mais respostas aprendidas independentemente. Objetivo: avaliar a influência da ayahuasca nesse processo. Metodologia: foram utilizados 12 ratos machos da linhagem wistar divididos em 3 grupos: crônico, agudo e controle. O delineamento foi dividido em: 1) habituação, 2) pré-teste (campo aberto e resolução), 3) treino das respostas pré-requisito, 4) pós-teste (campo aberto e resolução). A substância foi administrada via gavagem (2ml/kg) aos animais do grupo crônico da fase 4 à 6, e do grupo agudo nas fases 5 e 6. Os animais do grupo controle ingeriram água. Resultados: Não houve interferência na resolução, mas houve na aprendizagem das respostas, que foi mais lenta no grupo crônico. No campo aberto, houve uma diminuição da atividade locomotora e exploratória em animais sob efeito da droga.

UFR2709, a Nicotinic Acetylcholine Receptor Antagonist, Decreases Ethanol Intake in Alcohol-Preferring Rats.

Brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric acetylcholine-gated cation channels, have been suggested as molecular targets for the treatment of alcohol abuse and dependence. Here, we examined the effect of the competitive nAChR antagonist UFR2709 on the alcohol consumption of high-alcohol-drinking UChB rats. UChB rats were given free access to ethanol for 24-h periods in a two-bottle free choice paradigm and their ethanol and water intake were measured. The animals were i.p. injected daily for 17 days with a 10, 5, 2.5, or 1 mg/kg dose of UFR2709. Potential confounding motor effects of UFR2709 were assessed by examining the locomotor activity of animals administered the highest dose of UR2709 tested (10 mg/kg i.p.). UFR2709 reduced ethanol consumption and ethanol preference and increased water consumption in a dose-dependent manner. The most effective dose of UFR2709 was 2.5 mg/kg, which induced a 56% reduction in alcohol consumption. Administration of UFR2709 did not affect the weight or locomotor activity of the rats, suggesting that its effects on alcohol consumption and preference were mediated by specific nAChRs.

Involvement of D1- and D2-like dopamine receptors within the rat nucleus accumbens in the maintenance of morphine rewarding properties in the rats.

Previous studies on drug abuse have shown that response to drug-associated cues exist during prolonged abstinence. In succession to previous investigations in our laboratory on morphine dependence and our research on acquisition and expression phases of morphine-conditioned place preference (CPP), in this study we attempt to determine the effects of intraaccumbal administration of SCH-23390, as a D1-like receptor antagonist, and sulpiride, as a D2-like receptor antagonist, in the maintenance of morphine-induced CPP in rats. Seventy-nine adult male Wistar rats weighing 200-280 g were bilaterally implanted with cannulas into the nucleus accumbens. During the 3-day conditioning phase, the animals received daily subcutaneous administration of morphine (5 mg/kg). CPP score and locomotor activity of animals were recorded by Ethovision software. Different doses (0.25, 1, 4 μg per 0.5 μL vehicle) of D1- and D2-like antagonists were bilateral injected daily after the expression phase and during the extinction phase. Our findings revealed that intraaccumbal administration of D1-like and D2-like antagonists after the CPP test shortened the extinction phase in the rats. The results suggested that the existence of the dopamine receptors in the nucleus accumbens was important for the maintenance of morphine-rewarding properties during the extinction phase. Therefore, dopamine receptors may be considered as a promising therapeutic agent in preventing the maintenance of morphine-rewarding effects in dependent individuals. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The Effects of Neuropathic Pain on the State of Glial Cells and Hippocampal Neurogenesis in Old Animals

Abstract—We studied the effect of chronic neuropathic pain on the state of microglia and neurogenesis in the hippocampus in old mice. Neuropathic pain was induced by imposing three ligatures on the sciatic nerve of the right hind limb of animals. Testing behavior showed the presence of impaired working memory and locomotor activity in animals with neuropathic pain both in 1 week and 3 weeks after surgery. Behavioral disorders were accompanied by a decrease in hippocampal neurogenesis, as well as an increase in the expression of microglial markers Iba-1 and CD86 in the hippocampus of animals with a ligated sciatic nerve. In addition, the induction of neuropathic pain led to a change in the expression of astroglial markers S100β and GFAP in the hippocampus. The findings suggest that behavioral changes in neuropathic pain are accompanied by changes in the activity of microglia and astroglia, which leads to disruption of neurogenesis and a decrease in cognitive functions.

Effects of the colour of photophase light on locomotor activity in a nocturnal and a diurnal South African rodent.

Many physiological and behavioural responses to varying qualities of light, particularly during the night (scotophase), have been well documented in rodents. We used varying wavelengths of day-time (photophase) lighting to assess daily responses in locomotor activity in the nocturnal Namaqua rock mouse (Micaelamys namaquensis) and diurnal four-striped field mouse (Rhabdomys pumilio). Animals were exposed to three light-dark cycle regimes: a short-wavelength- (SWLC, blue), a medium-wavelength- (MWLC, green) and a long-wavelength light-dark cycle (LWLC, red). Overall, daily locomotor activity of both species changed according to different wavelengths of light: the diurnal species displayed most activity under the SWLC and the nocturnal species exhibited the highest levels of activity under the LWLC. Both species showed an increase in diurnal activity and a decrease in nocturnal activity under the LWLC. These results indicate an attenuated responsiveness to long-wavelength light in the nocturnal species, but this does not appear to be true for the diurnal species. These results emphasize that the effect of light on the locomotor activity of animals depends on both the properties of the light and the temporal organization of activity of a species.

Antinociceptive and antidepressive efficacies of the combined ineffective doses of S-ketamine and URB597.

Clinical studies have demonstrated that the NMDA receptor antagonist ketamine produces rapid antidepressant responses. There are safety concerns and adverse effects that limit the utilization of ketamine in psychiatry. Some studies have suggested combination therapy for optimal ketamine use. In this study, we evaluated the potential for combination therapy of ineffective doses of ketamine and fatty acid amide hydrolase inhibitor URB597 for the treatment of depression and pain in male NMRI mice. Intraperitoneal administration of ketamine (10mg/kg) at the time intervals of 115, 145, and 160min and ketamine (5mg/kg) at the time interval of 160min after administration increased the tail-flick latency, indicating an antinociceptive effect. The same doses of ketamine decreased immobility time in the forced swim test (FST), showing an antidepressant-like effect. Moreover, URB597 at the doses of 0.5 and 1mg/kg induced an antinociceptive effect, while it at the dose of 1mg/kg produced an antidepressant-like response. Furthermore, co-administration of the ineffective doses of ketamine (2.5mg/kg) and URB597 (0.1mg/kg) caused antinociceptive and antidepressant-like effects, while each one of them alone did not alter the performance of mice in the FST and tail-flick tests. It should be noted that none of the treatments alter animal locomotor activity compared to the control group. Therefore, the combined administration of ineffective doses of ketamine and URB597 might be an effective strategy in the therapy of depression and pain.

Non-coding cis-element of Period2 is essential for maintaining organismal circadian behaviour and body temperature rhythmicity

Non-coding cis-regulatory elements are essential determinants of development, but their exact impacts on behavior and physiology in adults remain elusive. Cis-element-based transcriptional regulation is believed to be crucial for generating circadian rhythms in behavior and physiology. However, genetic evidence supporting this model is based on mutations in the protein-coding sequences of clock genes. Here, we report generation of mutant mice carrying a mutation only at the E′-box cis-element in the promoter region of the core clock gene Per2. The Per2 E′-box mutation abolishes sustainable molecular clock oscillations and renders circadian locomotor activity and body temperature rhythms unstable. Without the E′-box, Per2 messenger RNA and protein expression remain at mid-to-high levels. Our work delineates the Per2 E′-box as a critical nodal element for keeping sustainable cell-autonomous circadian oscillation and reveals the extent of the impact of the non-coding cis-element in daily maintenance of animal locomotor activity and body temperature rhythmicity.

Оценка корректирующего влияния сульпирида на поведенческие нарушения алкоголизированных самцов белых крыс с разным уровнем депрессивности

The aim of the study was to evaluate correction of behavioral disorders with sulpiride, a dopamine autoreceptor inhibitor, in alcoholized rats taking into account individual typological features of the animals. Methods. Experiments were performed on sexually mature male rats weighing 180-220 g. The level of anxiety was determined in the elevated plus-maze by the total time of stay in and number of exits from the open space of the maze during 5 minutes of testing. Locomotor and exploratory activity and grooming behavior were assessed in the open field for 5 minutes. The severity of animal depression was determined using the standard Porsolt test by the number and total duration of immobility periods. The emotional state of animals was evaluated by the number of fecal boluses. After the initial (control) tests, the rats were divided into three subgroups based on the severity of depression as determined in the Porsolt test. Alcoholism was modeled by intraperitoneal injections of 10% ethanol (2 g/kg body weight) for 14 days. Then the animal behavior was re-tested. Sulpiride (Eglonyl, Sanofi Winthrop Industrie, France) was administered for 14 days at a dose of 10 mg/kg, intraperitoneally; then the animals were tested again. Results. Two-week alcoholization resulted in increased anxiety and depression of rats with low and medium depression degree at baseline. These disorders were evident from shortened stay of these animals in the open space of elevated plus-maze, reduced number of repeated exits from the open space, and a significant increase in the total time of immobility in the Porsolt test. The subsequent sulpiride treatment corrected the anxiogenic and depressogenic effects of alcoholism in male rats of these subgroups. Originally high-depressive animals did not show a sensitivity to the 14 day-administration of ethanol and subsequent inhibition of D2/D3-dopamine receptors in the elevated plus-maze and Porsolt test. Administration of ethanol for 14 days suppressed both the exploratory activity of rats in the open field regardless of their baseline degree of depression, and the locomotor activity of low-depressive animals. The subsequent sulpiride treatment did not abolish the effect of alcohol on the behavioral activity in the open field. Low-depressive alcoholized males developed a depression-like condition characterized by a marked behavioral deficit in the open field. The two-week alcoholization resulted in a significant (2-3.5 times) increase in the emotionality irrespective of the baseline degree of depression. This disorder was fully corrected by the sulpiride treatment in high-depressive rats and partially reduced the signs of emotionality in low- and medium-depressive animals. Conclusion. The study showed a possibility for correction of anxiety and depressive disorders induced by two weeks of modeled alcohol abuse with sulpiride depending on individual typological features of animals.

The Study of Cognitive-Stimulating Activity of Fluorinated Tetrahydrocarbazole Derivatives and Behavioral Responses in Transgenic Tg6799 Mice with Alzheimer’s Disease

The cognitive-stimulating, neuroprotective effects of promising fluorinated tetrahydrocarbazole derivatives (CA-7043x and CA-7050x) on the hippocampus-dependent memory of outbred mice (CD1) and transgenic Tg6799 mice, as well as their effect on anxiety, locomotor activity, and orienting-exploratory behavior of animals, were studied. It was found that both compounds have a pronounced cognitive-stimulating effect on CD1 mice, but do not show neuroprotective effects on memory support in Tg6799 mice. It is noted that, in the open-field test, the CA-7050x compound has a positive effect on the orientating behavior, and the CA-7043x compound has a positive effect on the exploratory response in the nontransgenic control.

Evaluation of the pharmacological involvement of ATP-sensitive potassium (KATP) channels in the antidepressant-like effects of topiramate on mice.

Acute doses of topiramate (TPM) have been shown to reduce immobility time in the mice forced swimming test (FST) through inhibition of the nitric oxide (NO) pathway. Adenosine triphosphate-sensitive potassium (KATP) channels are known to have an active role in depression. This study investigates the potential participation of KATP channels in the antidepressant-like effect of TPM through the stimulatory effects of NO. FST and tail suspension tests (TST) were applied to adult male mice for assessment of the antidepressant-like activity of TPM. Different doses of glibenclamide and cromakalim were also applied in order to investigate the involvement of KATP channels. Fluoxetine was used as a positive control for evaluation of antidepressant-like effects. In addition, each animal's locomotor activity was evaluated by the open-field test (OFT). TPM (30mg/kg intraperitoneal (i.p.)) had a significant reductive effect on the immobility behavior similar to fluoxetine (20mg/kg). Co-administration of sub-effective doses of glibenclamide (1mg/kg i.p.) and TPM (10mg/kg i.p.) led to significant synergistic effects in FST and TST. Additionally, the results showed that administration of the sub-effective dose of cromakalim (0.1 and 0.3mg/kg i.p.) blocked the antidepressant-like effects of TPM (30mg/kg i.p.) in both tests. These interventions had no impact on the locomotor movement of mice in OFT. This study shows that the antidepressant-like activity of TPM may potentially be mediated by the blocking of the KATP channels.

Histamine H3 receptor antagonist E177 attenuates amnesia induced by dizocilpine without modulation of anxiety-like behaviors in rats.

BackgroundAlzheimer disease (AD) is the main cause of dementia in elderly people. The potential of histamine H3 receptor (H3R) antagonists as a pharmacological treatment of several neuropsychiatric diseases is well established.MethodsThe novel non-imidazole-based H3R antagonist E177 was screened for its pro-cognitive effects on the inhibitory avoidance paradigm (IAP) and novel object recognition (NOR) task in a dizocilpine (DIZ)-induced model of amnesia in male Wistar rats. Donepezil, an acetylcholine esterase inhibitor, was used as the reference drug.ResultsAcute systemic treatment with E177 (1.25, 2.5, 5, and 10 mg/kg intraperitoneally [i.p.]) significantly attenuated the cognitive impairments induced by DIZ in the IAP (all P-values <0.05, n=7), and the protective effect of the most promising dose of E177 (5 mg/kg) was abrogated when H3R agonist R-(α)-methylhistamine (RAMH; 10 mg/kg i.p.) was co-administered (P=0.281 for DIZ-amnesia group vs DIZ + E177 + RAMH group, n=7). The discrimination index calculated for E177 (5 mg/kg, i.p.) showed a significant memory-enhancing effect on DIZ-induced short-term memory impairment in the NOR task (P<0.05, n=6), with the enhancement nullified when animals were co-administered RAMH (10 mg/kg). Moreover, the results revealed that E177 (5 and 10 mg/kg, i.p.) did not alter the anxiety levels and locomotor activity of animals naïve to the open-field test (all P-values >0.05, n=8) or the elevated plus maze test (all P-values >0.05, n=6–8), which indicated that the E177-induced enhancement of memory performance in the IAP or NOR task was unrelated to changes in emotional response or in spontaneous locomotor activity.ConclusionThe observed results suggested a possible contribution of H3Rs in the alteration of brain neurotransmitters that accompany neurodegenerative diseases, such as AD.

Effects of chronic lithium exposure in a modified rodent ketamine-induced hyperactivity model of mania

Bipolar illness is characterized by periods of “mania” — high energy, irritability, and increased psychomotor activation. While the neurobiological investigation of mania has been limited by the lack of reliable animal models, researchers have recently reported that daily subanesthetic doses of ketamine produce a lithium-reversible increase in rodent locomotor activity. Such studies have typically employed short-term (2 week) exposure to daily intraperitoneal-injected lithium and extremely brief (i.e., 5-min) open-field tests of hyperactivity. To increase the translational utility of the model, the effects of 70-days of orally administered lithium were examined on ketamine-induced hyperlocomotion during 30-min test sessions. Rats consumed 2.0 mEq/kg lithium chloride (LiCl) presented daily in a high incentive food (10 g of peanut butter). Control animals ingested peanut butter infused with an equimolar concentration of sodium chloride (NaCl). After 60 days of treatment, a 30-min baseline revealed no differences in the locomotor activity of LiCl and NaCl animals. During the next 10 days, animals received single daily supplemental injections of 25 mg/kg IP ketamine. A subset of animals was injected daily with saline and served as non-ketamine controls. Behavioral testing on the final two days of treatment confirmed that ketamine administration produced a profound increase in locomotor activity that was significantly attenuated in the LiCl group. Additionally, blood plasma levels of lithium were found to be comparable to low-moderate human therapeutic levels. These data confirm the viability and utility of ketamine-induced hyperlocomotion as a rodent model of mania.

Continuous measurement of locomotor activity during convalescence and acclimation in group-housed rats

Locomotor activity is affected by a range of factors in addition to experimental treatment, including the breeding environment. Appropriate convalescence and acclimation are important for animal experiments, because environmental changes and physical burden can result from surgery, transportation, and cage exchange. However, the duration that locomotor activity is affected by these factors is currently unclear, because it has traditionally been difficult to measure locomotor activity in multiple group-housed animals in any location other than the analysis room. In the present study, we analyzed the locomotor activity of group-housed rats using a nano tag® after surgery, transportation, and cage exchange. The nano tag®, a new device for analyzing activity, can measure locomotor activity in laboratory animals with no limitation on the number of animals in same cage. Any type of cage can be used for analysis, at any time of day, and in any location. Nano tags® were subcutaneously implanted in male rats (F344/NSlc, 6 weeks of age) and locomotor activity was continuously measured after surgery, transportation, and cage exchange. Significant activity changes were observed in rats after transportation and cage exchange, 9 days and 3 h after the event, respectively. The results suggest that continuous measurement of locomotor activity with nano tags® can be used to monitor changes in activity induced by environmental changes, and will be helpful for designing animal experiments analyzing locomotor activity.

Evaluation and comparison of the antidepressant-like activity of Artemisia dracunculus and Stachys lavandulifolia ethanolic extracts: an in vivo study.

Several studies have supported the preventive and therapeutic values of phenolic compounds including chlorogenic acid, syringic acid, vanillic acid, ferulic acid, caffeic acid, luteolin, rutin, catechin, kaempferol, and quercetin in mental disorders. Since these secondary metabolites are reported as the phenolic compounds of Artemisia dracunculus (A. dracunculus) and Stachys lavandulifolia (S. lavandulifolia), the main aim of this study was the evaluation and comparison of the phenolic contents, flavonoids, and antidepressant-like activity of Artemisia dracunculus with Stachys lavandulifolia. Antidepressant-like activity of the extracts was evaluated in the forced swimming test (FST) and the tail suspension test (TST). Moreover, the open field test was conducted to evaluate the general locomotor activity of mice following treatment with the extracts. Since phenolic compounds and flavonoids play main roles in pharmacological effects, the phenolic and flavonoid contents of the extracts were measured. Though significant difference between the phenolic contents of the extracts was not observed, but S. lavandulifolia exhibited higher flavonoid contents. Animal treatment with extracts decreased the immobility times in both FST and TST compared to the vehicle group without any significant effect on the locomotor activity of animals. Also, S. lavandulifolia at 400 mg/kg showed higher potency in both tests compared to A. dracunculus. Our results provided promising evidence on the antidepressant-like activity of both extracts which could be related to flavonoids as the main components of the extracts, but more studies need to be conducted to specify the main compounds and the mechanisms involved in the observed effects.

Age-associated changes in waking hippocampal sharp-wave ripples.

Hippocampal sharp-wave ripples are brief high-frequency (120-250 Hz) oscillatory events that support mnemonic processes during sleep and awake behavior. Although ripples occurring during sleep are believed to facilitate memory consolidation, waking ripples may also be involved in planning and memory retrieval. Recent work from our group determined that normal aging results in a significant reduction in the peak oscillatory frequency and rate-of-occurrence of ripples during sleep that may contribute to age-associated memory decline. It is unknown, however, how aging alters waking ripples. We investigated whether characteristics of waking ripples undergo age-dependent changes. Sharp-wave ripple events were recorded from the CA1 region of the hippocampus in old (n = 5) and young (n = 6) F344 male rats as they performed a place-dependent eyeblink conditioning task. Several novel observations emerged from this analysis. First, although aged rats expressed more waking ripples than young rats during track running and reward consumption, this effect was eliminated, and, in the case of track-running, reversed when time spent in each location was accounted for. Thus, aged rats emit more ripples, but young rats express a higher ripple rate. This likely results from reduced locomotor activity in aged animals. Furthermore, although ripple rates increased as young rats approached rewards, rates did not increase in aged rats, and rates in aged and young animals were not affected by eyeblink conditioning. Finally, although the oscillatory frequency of ripples was lower in aged animals during rest, frequencies in aged rats increased during behavior to levels indistinguishable from young rats. Given the involvement of waking ripples in memory retrieval, a possible consequence of slower movement speeds of aged animals is to provide more opportunity to replay task-relevant information and compensate for age-related declines in ripple rate during task performance.

Electrographic spikes are common in wildtype mice

High-voltage rhythmic electroencephalographic (EEG) spikes have been recorded in wildtype (WT) rats during periods of light slow-wave sleep and passive wakefulness. The source of this activity is unclear but has been attributed to either an inherent form of absence epilepsy or a normal feature of rodent sleep EEG. In contrast, little is known about epileptiform spikes in WT mice. We thus characterize and quantify epileptiform discharges in WT mice for the first time. Thirty-six male WT C57 mice with 24-h wireless telemetry video-EEG recordings were manually scored by blinded reviewers to mark individual spikes and spike trains. Epileptiform spikes were detected in 100% of the recorded WT mice, and spike trains of at least three spikes were recorded in 90% of mice. The spikes were more frequent during the day than at night and were inversely correlated to each animal's locomotor activity. However, the discharges were not absent during active nighttime periods. These discharges may indicate a baseline tendency toward epileptic seizures or perhaps are benign variants of normal rodent background EEG. Nevertheless, a better understanding of baseline WT EEG activity will aid in differentiating pathological and normal EEG activity in mouse epilepsy models.

Intra-hippocampal administration of orexin receptor antagonists dose-dependently attenuates reinstatement of morphine seeking behavior in extinguished rats

It has been shown that the hippocampus plays an essential role in the regulation of reward and memory as indicated by the conditioned place preference (CPP) paradigm. Morphine-induced CPP is a common method to consider motivational properties of morphine in animals. Recently, this model has been used in many laboratories to investigate neuronal mechanisms underlying reinstatement of morphine seeking induced by drug re-exposure. Our previous studies indicate that the hippocampus especially CA1 region is involved in reinstatement of drug-seeking behaviors. Also, several studies have shown that orexin attenuates key functional and behavioral effects of its co-transmitter dynorphin. The present study evaluates the role of orexinergic receptors within the CA1 region of the hippocampus in the reinstatement of morphine-induced CPP. Therefore, after the extinction period, the different doses (SB 334867; 0.3, 3, and 30 nM/0.5 μl DMSO) of either orexin-1 or -2 receptor antagonists were bilaterally microinjected into the CA1, 15 min before receiving an effective priming dose of morphine (1 mg/kg). The results revealed that administration of both SB 334867 and TCS OX2 29 prior to injection of the priming dose of morphine significantly reduced the reinstatement of morphine-induced CPP without altering the animal's locomotor activity. Also, the 50% effective dose value of SB 334867 on the reinstatement of morphine seeking behavior was close three times more than that in TCS OX2 29 treatment group. Therefore, the consequences suggested that both orexin receptors in the CA1 play a considerable role in the reinstatement of morphine-induced CPP.

Monoaminergic Involvement in Decreased Locomotor Activity of Mice Treated with α and β-amyrin from Protium heptaphyllum

A triterpenic mixture of α and β-amyrin (AMY) extracted from Protium heptaphyllum has demonstrated several pharmacological effects, including activity in the central nervous system. The aim of this study was to evaluate the effect of AMY administration on locomotor activity of mice by the open field test using some monoaminergic agonists and antagonists and the cerebral cortex levels of monoamines and their major metabolites by high-performance liquid chromatography. Mice were treated acutely with AMY at doses of 1, 2.5 and 5 mg/kg given intraperitoneally and with the pharmacological agents and placed in open field test, then the animals were sacrificed and the cerebral cortex extracted, and monoamines were assayed in tissue homogenates. AMY at 1, 2.5 and 5 mg/kg decreased locomotor activity of animals by 25, 31 and 39%, respectively in the open field test. Ondasentron, doxazosin, oxymetazoline and clonidine did not reverse the inhibitory effect of 5 mg/kg AMY. Venlafaxine and yohimbine reversed the inhibitory effect of 5 mg AMY. In the cortex, the 5-HT and 5-HIAA were significantly reduced by the administration of AMY. NE and HVA were also reduced with 2.5 and 5 mg/kg AMY, while Dopamine and DOPAC were not increased with AMY. In conclusion, AMY decreased locomotor activity of animals accompanied by a decrease in 5-HT and NE levels in the cerebral cortex, this locomotor effect is reversed by drug that blocker the α-2-adrenoreceptor.