RATIONALE: Development of new drugs for treatment of Alzheimer's disease (AD) requires valid paradigms for testing their efficacy and sensitive tests validated in translational research. OBJECTIVES: We present validation of a place-navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM), in comparable animal and human protocols. METHODS: We used scopolamine to model cognitive dysfunction similar to that seen in AD and donepezil, a symptomatic medication for AD, to assess its potential reversible effect on this scopolamine-induced cognitive dysfunction. We tested the effects of scopolamine and the combination of scopolamine and donepezil on place navigation and compared their effects in human and rat versions of the HGT. Place navigation testing consisted of 4 sessions of HGT performed at baseline, 2, 4, and 8 h after dosing in humans or 1, 2.5, and 5 h in rats. RESULTS: Scopolamine worsened performance in both animals and humans. In the animal experiment, co-administration of donepezil alleviated the negative effect of scopolamine. In the human experiment, subjects co-administered with scopolamine and donepezil performed similarly to subjects on placebo and scopolamine, indicating a partial ameliorative effect of donepezil. CONCLUSIONS: In the task based on the MWM, scopolamine impaired place navigation, while co-administration of donepezil alleviated this effect in comparable animal and human protocols. Using scopolamine and donepezil to challenge place navigation testing can be studied concurrently in animals and humans and may be a valid and reliable model for translational research, as well as for preclinical and clinical phases of drug trials.

• MeSH
• antagonisté muskarinových receptorů farmakologie   MeSH
• bludiště - učení účinky léků   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• indany farmakologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• mladý dospělý MeSH
• piperidiny farmakologie   MeSH
• potkani Wistar MeSH
• prostorová navigace účinky léků   MeSH
• skopolamin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

In the present study we investigated the sex differences in the effect of adult long-term drug treatment on cognitive functions of Wistar rats, which were prenatally exposed to MA (5mg/kg) or saline. Cognitive functions were tested as an ability of spatial learning in the Morris Water Maze (MWM), which consisted of three types of tests: "Place Navigation Test"; "Probe Test", and "Memory Recall Test". Adult animals were injected daily, after completion of the last trial, either with saline or cocaine (COC; 5mg/kg), MDMA (3,4-methylenedioxy-methamphetamine; 5mg/kg), morphine (MOR; 5mg/kg), or delta-9-tetrahydrocannabinol (THC; 2mg/kg). Results revealed worsened MWM performance in female rats after drug treatment in adulthood. Not only were traditionally investigated parameters affected by drug treatment (latency of platform acquisition, search strategy, distance traveled), but also strategies used by animals (thigmotaxis, scanning). Analyses of search strategies observed in the Place Navigation Test, as well as in the Memory Recall Test, demonstrated variations in the percentage of time spent in thigmotaxis and scanning in females after treatment with COC, MDMA, MOR, and THC. Although we did not see a sensitizing effect of prenatal MA, in some cases the effect of drug treatment in adulthood differed depending on the prenatal drug exposure. The data presented in this study demonstrates that exposure to drugs with various mechanisms of action alters spatial abilities of female rats in the MWM. Alterations in the effect of adult drug treatment with reference to prenatal drug exposure were also found in the present study.

• MeSH
• kognice účinky léků   MeSH
• kokain farmakologie   MeSH
• methamfetamin toxicita   MeSH
• morfin farmakologie   MeSH
• N-methyl-3,4-methylendioxyamfetamin farmakologie   MeSH
• náhodné rozdělení MeSH
• pohlavní dimorfismus * MeSH
• potkani Wistar MeSH
• prostorová navigace účinky léků   MeSH
• prostorové učení účinky léků   MeSH
• psychologické testy MeSH
• psychotropní léky farmakologie   MeSH
• těhotenství MeSH
• tetrahydrokanabinol farmakologie   MeSH
• zpožděný efekt prenatální expozice psychologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články 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