Methamphetamine abuse imposes a significant burden on individuals and society worldwide, and an effective therapy of methamphetamine addiction would provide distinguished social benefits. Ghrelin significantly participates in reinforcing neurobiological mechanisms of stimulants, including amphetamines; thus, ghrelin antagonism is proposed as a promising addiction treatment. The aim of our study was to elucidate whether the pretreatment with growth hormone secretagogue receptor (GHS-R1A) antagonist, substance JMV2959, could reduce the methamphetamine intravenous self-administration (IVSA) and the tendency to relapse, and whether JMV2959 could reduce or prevent methamphetamine-induced conditioned place preference (CPP) in rats. Following an adequate maintenance period, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 180 min sessions of methamphetamine IVSA under a fixed ratio FR1, which significantly reduced the number of active lever-pressings, the number of infusions, and the amount of the consumed methamphetamine dose. Pretreatment with JMV2959 also reduced or prevented relapse-like behavior tested in rats on the 12th day of the abstinence period. Pretreatment with JMV2959 significantly reduced the expression of methamphetamine-induced CPP. Simultaneous administration of JMV2959 with methamphetamine during the conditioning period significantly reduced the methamphetamine-CPP. Our results encourage further research of the ghrelin antagonism as a potential new pharmacological tool for methamphetamine addiction treatment.

• MeSH
• analýza rozptylu MeSH
• autoaplikace MeSH
• časové faktory MeSH
• glycin aplikace a dávkování   analogy a deriváty   farmakologie   MeSH
• intravenózní podání MeSH
• methamfetamin aplikace a dávkování   farmakologie   MeSH
• podmiňování (psychologie) účinky léků   MeSH
• potkani Wistar MeSH
• prostorové chování účinky léků   MeSH
• receptory ghrelinu antagonisté a inhibitory   metabolismus   MeSH
• stimulanty centrálního nervového systému aplikace a dávkování   farmakologie   MeSH
• tělesná hmotnost účinky léků   MeSH
• triazoly aplikace a dávkování   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

We used the psychotomimetic phencyclidine (PCP) to investigate the relationships among cognitive behavior, coordinated neural network function, and information processing within the hippocampus place cell system. We report in rats that PCP (5 mg/kg, i.p.) impairs a well learned, hippocampus-dependent place avoidance behavior in rats that requires cognitive control even when PCP is injected directly into dorsal hippocampus. PCP increases 60-100 Hz medium-freguency gamma oscillations in hippocampus CA1 and these increases correlate with the cognitive impairment caused by systemic PCP administration. PCP discoordinates theta-modulated medium-frequency and slow gamma oscillations in CA1 LFPs such that medium-frequency gamma oscillations become more theta-organized than slow gamma oscillations. CA1 place cell firing fields are preserved under PCP, but the drug discoordinates the subsecond temporal organization of discharge among place cells. This discoordination causes place cell ensemble representations of a familiar space to cease resembling pre-PCP representations despite preserved place fields. These findings point to the cognitive impairments caused by PCP arising from neural discoordination. PCP disrupts the timing of discharge with respect to the subsecond timescales of theta and gamma oscillations in the LFP. Because these oscillations arise from local inhibitory synaptic activity, these findings point to excitation-inhibition discoordination as the root of PCP-induced cognitive impairment.SIGNIFICANCE STATEMENT Hippocampal neural discharge is temporally coordinated on timescales of theta and gamma oscillations in the LFP and the discharge of a subset of pyramidal neurons called "place cells" is spatially organized such that discharge is restricted to locations called a cell's "place field." Because this temporal coordination and spatial discharge organization is thought to represent spatial knowledge, we used the psychotomimetic phencyclidine (PCP) to disrupt cognitive behavior and assess the importance of neural coordination and place fields for spatial cognition. PCP impaired the judicious use of spatial information and discoordinated hippocampal discharge without disrupting firing fields. These findings dissociate place fields from spatial cognitive behavior and suggest that hippocampus discharge coordination is crucial to spatial cognition.

• MeSH
• fencyklidin aplikace a dávkování   toxicita   MeSH
• halucinogeny aplikace a dávkování   toxicita   MeSH
• hipokampální oblast CA1 účinky léků   patofyziologie   MeSH
• injekce intraventrikulární MeSH
• krysa rodu rattus MeSH
• lokomoce účinky léků   fyziologie   MeSH
• nervová síť účinky léků   patofyziologie   MeSH
• potkani Long-Evans MeSH
• prostorové chování účinky léků   fyziologie   MeSH
• učení vyhýbat se účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Although animals often learn and monitor the spatial properties of relevant moving objects such as conspecifics and predators to properly organize their own spatial behavior, the underlying brain substrate has received little attention and hence remains elusive. Because the anterior cingulate cortex (ACC) participates in conflict monitoring and effort-based decision making, and ACC neurons respond to objects in the environment, it may also play a role in the monitoring of moving cues and exerting the appropriate spatial response. We used a robot avoidance task in which a rat had to maintain at least a 25cm distance from a small programmable robot to avoid a foot shock. In successive sessions, we trained ten Long Evans male rats to avoid a fast-moving robot (4cm/s), a stationary robot, and a slow-moving robot (1cm/s). In each condition, the ACC was transiently inactivated by bilateral injections of muscimol in the penultimate session and a control saline injection was given in the last session. Compared to the corresponding saline session, ACC-inactivated rats received more shocks when tested in the fast-moving condition, but not in the stationary or slow robot conditions. Furthermore, ACC-inactivated rats less frequently responded to an approaching robot with appropriate escape responses although their response to shock stimuli remained preserved. Since we observed no effect on slow or stationary robot avoidance, we conclude that the ACC may exert cognitive efforts for monitoring dynamic updating of the position of an object, a role complementary to the dorsal hippocampus.

• MeSH
• agonisté receptorů GABA-A farmakologie   MeSH
• cingulární gyrus účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• muscimol farmakologie   MeSH
• neurony účinky léků   fyziologie   MeSH
• podněty MeSH
• potkani Long-Evans MeSH
• pozornost účinky léků   fyziologie   MeSH
• prostorové chování účinky léků   fyziologie   MeSH
• reakční čas fyziologie   MeSH
• učení vyhýbat se účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Drug development for Alzheimer disease (AD) is challenged by the success in animal models tested in the Morris water maze (MWM) and the subsequent failures to meet primary outcome measures in phase II or III clinical trials in patients. The human variant of MWM (hMWM) enables us to examine allocentric and egocentric navigation as in the MWM. OBJECTIVE: It was the aim of this study to examine the utility of a computerized hMWM to assess the effects of donepezil in mild AD. METHODS: Donepezil 5 mg/day was started after initial hMWM testing in the treated group (n = 12), and after 28 days, the dose was increased to 10 mg/day. The performance after 3 months was compared to that of a non-treated group (n = 12). RESULTS: Donepezil stabilized or improved the spatial navigation performance after 3 months, especially in the allocentric delayed recall subtask (p = 0.014). CONCLUSIONS: The computerized hMWM has the potential to measure the effects of donepezil in mild AD. It is a sensitive cognitive outcome measure in AD clinical trials.

• MeSH
• Alzheimerova nemoc farmakoterapie   MeSH
• cholinesterasové inhibitory terapeutické užití   MeSH
• indany terapeutické užití   MeSH
• lidé MeSH
• neuropsychologické testy * MeSH
• pilotní projekty MeSH
• piperidiny terapeutické užití   MeSH
• počítače MeSH
• prostorové chování účinky léků   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

Cholinesterase inhibitors are beneficial in the treatment of Alzheimer's disease via indirect increase of cholinergic neuro-transmission. The aim of the present study was to evaluate the potency of inhibitors tacrine, rivastigmine and donepezil to reverse cholinergic depletion induced by 3-quinuclidinyl benzilate (QNB, 2 mg kg−1) in Wistar rats performing the multiple T-maze test. The effect of QNB on retention was compared to the effect of standard amnesic drug, scopolamine, at the dose of 0.3 mg kg−1. Well-trained rats were treated intra-peritoneally with QNB, followed by another injection containing saline or tacrine (10 mg kg−1) or rivastigmine (1.2 mg kg−1) or donepezil (2.65 mg kg−1) 15 min later. Rats were subjected to the T-maze task 30 min and 24 h following QNB administration. The passage time and number of errors were observed. QNB significantly impaired the performance of rats in both tested times in contrast to short-lasting effect of scopolamine (30 min only). The inhibitors rivastigmine and donepezil significantly attenuated QNB-induced behavioural impairment in the 30 min tests, whereas tacrine failed to have the same effect. Moreover, the performance of tacrine-treated rats was worse due to cholinergic over-stimulation. Beneficial effects of all tested inhibitors including tacrine were evident in the 24 h test.

• MeSH
• acetylcholin fyziologie   nedostatek   MeSH
• Alzheimerova nemoc farmakoterapie   MeSH
• bludiště - učení účinky léků   MeSH
• chinuklidinylbenzilát farmakologie   škodlivé účinky   MeSH
• cholinesterasové inhibitory * farmakologie   terapeutické užití   MeSH
• fenylkarbamáty farmakologie   terapeutické užití   MeSH
• indany farmakologie   terapeutické užití   MeSH
• kognice účinky léků   MeSH
• krysa rodu rattus fyziologie   MeSH
• nervový přenos účinky léků   MeSH
• piperidiny farmakologie   terapeutické užití   MeSH
• potkani Wistar fyziologie   MeSH
• prostorová navigace účinky léků   MeSH
• prostorové chování * účinky léků   MeSH
• statistika jako téma MeSH
• takrin farmakologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus fyziologie   MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Psychostimulants have been shown to affect brain regions involved in the process of learning and memory consolidation. It has been shown that females are more sensitive to the effects of drugs than males. The aim of our study was to investigate how prenatal methamphetamine (MA) exposure and application of amphetamine (AMP) in adulthood would affect spatial learning of adult female and male rats. Mothers of the tested offspring were exposed to injections of MA (5mg/kg) or saline (SA) throughout the entire gestation period. Cognitive functions of adult rats were evaluated in the Morris Water Maze (MWM) tests. Adult offspring were injected daily with AMP (5mg/kg) or SA through the period of MWM testing. Our data from the MWM tests demonstrates the following. Prenatal MA exposure did not change the learning ability of adult male and female rats. However, AMP administration to adult animals affected cognitive function in terms of exacerbation of spatial learning (increasing the latency to reach the hidden platform, the distance traveled and the search error) only in female subjects. There were sex differences in the speed of swimming. Prenatal MA exposure and adult AMP treatment increased the speed of swimming in female groups greater than in males. Overall, the male subjects showed a better learning ability than females. Thus, our results indicate that the adult AMP treatment affects the cognitive function and behavior of rats in a sex-specific manner, regardless of prenatal exposure.

• MeSH
• amfetamin farmakologie   MeSH
• bludiště - učení účinky léků   MeSH
• kognice účinky léků   MeSH
• krysa rodu rattus MeSH
• methamfetamin aplikace a dávkování   toxicita   MeSH
• potkani Wistar MeSH
• prostorové chování účinky léků   MeSH
• sexuální faktory MeSH
• stimulanty centrálního nervového systému aplikace a dávkování   toxicita   MeSH
• těhotenství MeSH
• věkové faktory MeSH
• zpožděný efekt prenatální expozice chemicky indukované   psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Spatial navigation and memory is considered to be a part of the declarative memory system and it is widely used as an animal model of human declarative memory. However, spatial tests typically involve only static settings, despite the dynamic nature of the real world. Animals, as well as people constantly need to interact with moving objects, other subjects or even with entire moving environments (flowing water, running stairway). Therefore, we design novel spatial tests in dynamic environments to study brain mechanisms of spatial processing in more natural settings with an interdisciplinary approach including neuropharmacology. We also translate data from neuropharmacological studies and animal models into development of novel therapeutic approaches to neuropsychiatric disorders and more sensitive screening tests for impairments of memory, thought, and behavior.

• MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• látky ovlivňující centrální nervový systém farmakologie   MeSH
• lidé MeSH
• mozek účinky léků   fyziologie   MeSH
• paměť účinky léků   fyziologie   MeSH
• prostorové chování účinky léků   fyziologie   MeSH
• racionální návrh léčiv * MeSH
• vnímání prostoru účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Spatial navigation attracts the attention of neuroscientists as an animal analogue of human declarative memory. The Carousel maze is a dry-land navigational paradigm, which proved to be useful in studying neurobiological substrates of learning. The task involves avoidance of a stable sector on a rotating arena and is highly dependent upon the hippocampus. The present study aims at testing hypothesis that sulpiride (a centrally-active dopamine D2-like receptor antagonist) and propranolol (a beta-blocker) impair spatial learning in the Carousel maze after combined systemic administration. These doses were previously shown to be subthreshold in this task. Results showed that both substances affected behavior and significantly potentiated their negative effects on spatial learning. This suggests central interaction of both types of receptors in influencing acquisition of this dynamic-environment task.

• MeSH
• antagonisté dopaminu D2 MeSH
• antagonisté dopaminu aplikace a dávkování   MeSH
• beta blokátory aplikace a dávkování   MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• potkani Long-Evans MeSH
• propranolol aplikace a dávkování   MeSH
• prostorové chování účinky léků   fyziologie   MeSH
• psychomotorický výkon účinky léků   fyziologie   MeSH
• receptory dopaminu D2 fyziologie   MeSH
• sulpirid aplikace a dávkování   MeSH
• synergismus léků MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Our previous studies demonstrated that methamphetamine administered during gestation and lactation periods impairs maternal behavior, alters the functional development of rat pups and affects behavior in adulthood. The aim of our study was to investigate the effect of prenatal methamphetamine exposure and cross-fostering on learning tested in Morris water maze (MWM) in adult male rats. Mothers were daily exposed to injection of methamphetamine (MA) (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postnatal day 1, pups were cross-fostered so that each mother received some of her own and some of the pups of mother with the opposite treatment. Based on the prenatal and postnatal treatments 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in MWM. Two types of tests were used: (1) “Place navigation test” (Learning) and (2) “Probe test” (Probe). In the test of learning, all animals fostered by methamphetamine-treated dams had longer latencies and trajectories, and bigger search error than the animals fostered by saline-treated control mother, regardless of prenatal exposure. Further, the animals prenatally exposed to methamphetamine swam slower than the animals prenatally exposed to saline, regardless of postnatal exposure in the test of learning and in the Probe test. Our results showed that neither prenatal nor postnatal methamphetamine exposure affected the Probe test. Our results showed that prenatal exposure to methamphetamine at dose of 5 mg/kg does not impair learning in the MWM, while postnatal exposure to methamphetamine from mothers’ breastmilk and maternal care of mother exposed to methamphetamine impairs learning of adult male rats. On the other hand, the maternal care of control mothers does not impair learning of rat pups prenatally exposed to methamphetamine. The present study demonstrates that cross-fostering may affect learning in adulthood.

• MeSH
• bludiště - učení fyziologie   účinky léků   MeSH
• embryonální a fetální vývoj fyziologie   MeSH
• experimenty na zvířatech MeSH
• financování organizované MeSH
• krysa rodu rattus MeSH
• methamfetamin analogy a deriváty   diagnostické užití   metabolismus   MeSH
• prostorové chování fyziologie   účinky léků   MeSH
• statistika jako téma MeSH
• zpožděný efekt prenatální expozice diagnóza   etiologie   MeSH
• Check Tag
• krysa rodu rattus MeSH
• Publikační typ
• grafy a diagramy MeSH

Animal models of neuropsychiatric disorders are current topics in behavioral neuroscience. Application of non-competitive antagonists of NMDA receptors (such as MK-801) was proposed as a model of schizophrenia, as it leads to specific behavioral alterations, which are partly analogous to human psychotic symptoms. This study examined an animal model of schizophrenia induced by a systemic application of MK-801 (0.15 and 0.20 mg/kg) into rats tested in the active allothetic place avoidance (AAPA) task. Previous studies suggested that MK-801 may interact in vivo with other neurotransmitter systems, including noradrenergic system. Our experiments therefore evaluated the hypothesis that both locomotor stimulation and deficit in avoidance behavior in AAPA task induced by this drug would be reversible by application of alpha1-adrenergic antagonist prazosin (1 and 2 mg/kg). The results showed that both doses of prazosin partially reversed hyperlocomotion induced by higher doses of MK-801 and an avoidance deficit measured as number of entrances into the shock sector. Interestingly, no effect of prazosin on the MK-801-induced decrease of maximum time between two entrances (another measure of cognitive performance) was observed. These results support previous data showing that prazosin can compensate for the hyperlocomotion induced by MK-801 and newly show that this partial reduction sustains even in the forced locomotor conditions, which are involved in the AAPA task. The study also shows that certain parameters of avoidance efficiency may be closely related to locomotor activity, whereas other measures of cognition may more selectively reflect cognitive changes.

• MeSH
• alfa blokátory farmakologie   MeSH
• antagonisté excitačních aminokyselin MeSH
• dizocilpinmaleát MeSH
• financování organizované MeSH
• krysa rodu rattus MeSH
• lokomoce účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• paměť účinky léků   MeSH
• potkani Long-Evans MeSH
• prazosin farmakologie   MeSH
• prostorové chování účinky léků   MeSH
• schizofrenie (psychologie) MeSH
• schizofrenie chemicky indukované   MeSH
• učení vyhýbat se účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH