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1

The involvement of cholinergic system in nicotine sensitization and cross - sensitization between nicotine and morphine in mice

100%

Staniak N. , Biala G.

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nr S

EN

The mesolimbic dopamine system, the main neural system mediating sensitization, seems to overlap this mediating reward. Given some data indicating that dopamine neurons are effected by cholinergic neurotransmitters, the aim of present study was to determine the influence of varenicline, a partial α4β2 nicotinic receptor agonist (0.5, 1 and 2 mg/kg) and mecamylamine, a nonselective nicotinic receptor antagonist (0.5, 1 and 2 mg/kg) on behavioural sensitization and cross – sensitization induced by nicotine (0.175 mg/kg, base) and morphine (5 mg/kg) in mice. First, we revealed that repeated injections of nicotine (9 days, every other day) produced significant increase in locomotor activity in mice measured following 7-day withdrowal after injection of challange doses of nicotine and morphine. Subsequently, we found that varenicline and mecamylamine attenuated the acquisition and expression of nicotine sensitization as well as locomotor crosssensitization between nicotine and morphine. Because they had no effects on naive mice, we concluded that the ability of both agents to block this results did not correspond to general supression of activity. The development of nicotine locomotor sensitization shows similarity to relapse described in ex-smokers and cross – sensitization seems to reflect the phenomenon of simultaneous abuse of several different drugs. Our results indicate similar nicotinic neurotransmission - probably through the α4β2 receptor subtypes - involved in the locomotor stimulant effects of nicotine and morphine in mice. This data suggest that cholinergic neurotransmission may be a potential target for developing pharmacotherapeutic strategies to prevent and treat nicotine and/or opioid addiction.

2

The motivational properties of selective dopamine D2/D3 receptor agonists studied with an operant procedure in rats

80%

Biala G. , Thiebot M. H. , Puech A.

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1997

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tom 57

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nr 5

3

The influence of fatty-acid amide hydrolase inhibitors on memory-related behaviors provoked by cholinergic receptor ligands in mice

80%

Kruk-Slomka M. , Dzik A. , Slomka T. , Biala G.

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nr Suppl.1

EN

INTRODUCTION: The endocannabinoid system (ECS) is composed of cannabinoid (CB: CB1 and CB2) receptors and endocannabinoids, which are degraded by fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Thus, the function of the ECS might be modulated in a direct way, through CB receptor ligands or indirectly by FAAH and MAGL inhibitors. The ECS system is involved in many physiological functions, also through interaction with many systems. The cholinergic system plays a crucial role in memory processes. A connection with the ECS, especially CB and cholinergic receptor ligands, is supported by a large body of research. However, the influence of the ECS through an indirect manner in the context of cognitive processes remains poorly understood. AIM(S): The aim of the study was to evaluate the indirect influence of ECS, using of FAAH (URB 597) and MAGL (JZL 184) inhibitors, on memory related effects provoked by cholinergic receptor ligands, a cholinergic receptor agonist, nicotine, and a cholinergic receptor antagonist, scopolamine, in mice. METHOD(S): We assessed different memory stages using the passive avoidance (PA) test. A deficit in PA performance was expressed as the difference between retention and training latencies and is taken as an index of latency (IL). RESULTS: Co-administration of non-effective dose of JZL 184 (4 mg/kg), but not URB 597 (0.1 mg/kg), with a non‑effective dose of nicotine (0.05 mg/kg) enhanced both acquisition and consolidation of memory in the PA test in mice. An acute injection of JZL 184 (4 mg/kg) attenuated pro‑cognitive effects induced by effective dose of nicotine (0.1 mg/kg). In turn, co‑administration of URB (0.1 mg), but not JZL 184 (4 mg/kg), with scopolamine (1 mg/kg) attenuated the scopolamine-induced memory impairment in the PA test in mice CONCLUSIONS: The present findings clearly indicate that the ECS, through an indirect manner, modulates memory processes, especially those in which cholinergic pathways are implicated.

4

Cross-reinstatement of nicotine-conditioned place preference in rats

80%

Budzynska B. , Kruk M. , Biala G.

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nr 3

5

Effects of the cannabinoid receptor ligands on anxiety-related effects of D-amphetamine and nicotine in the mouse elevated plus maze test

80%

Biala G. , Kruk M. , Budzynska B.

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nr 2

113-122

EN

The purpose of the experiments was to examine the anxiety-related effects of d-amphetamine and nicotine, and the possible involvement of the endocannabinoid system. D-amphetamine (2 mg/kg, ip) was administered acutely or daily for 8 days. On the 9th day, mice were challenged with d-amphetamine (2 mg/kg, ip) or nicotine (0.1 mg/kg, sc), and were tested in the elevated plus maze. Additionally, a distinct group of mice was pretreated with an acute (0.1 mg/kg, sc) or subchronic nicotine (6 days), and subjected to nicotine (0.1 mg/kg, sc) or d-amphetamine (2 mg/kg, ip) challenge on the 7th day. The cannabinoid receptor ligands, WIN 55,212-2, a non-selective cannabinoid receptor agonist (0.25; 0.5 and 1 mg/kg, ip) and rimonabant, a CB1 cannabinoid receptor antagonist (0.25; 0.5; 1 and 2 mg/kg, ip) were injected prior to each injection of saline or acute and subchronic d-amphetamine or nicotine. We observed that acute anxiogenic and subchronic anxiolytic effects of both psychostimulants as well as the development of full cross-tolerance to their anxiogenic effects were dose-dependently blunted by ineffective doses of WIN 55,212-2 (0.25 and 0.5 mg/kg) and rimonabant (0.5 and 1 mg/kg). These results provide evidence that the endogenous cannabinoid system is involved in the anxiety-related responses to d-amphetamine and/or nicotine.

6

Involvement of CB1 cannabinoid receptors in memory-related response induced by nicotine in mice

80%

Kruk M. , Budzynska B. , Biala G.

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nr 3

7

The involvement of the CB2 agonist in the behavioral and biochemical effects in the experimental animal models

80%

Kruk-Slomka M. , Budzynska B. , Boguszewska-Cubara A. , Biala G.

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nr 3

EN

Cannabinoids are implicated in regulation of variety emotions through the type 1 (CB1) and type 2 (CB2) receptors. Our pharamcological interests have been focused on the effects of CB2 receptor selective ligands in the treatment of Alzheimer disease (AD) which is associated with memory-loss, phobia, depression as well as oxidative processes in brain. We examined the impact of CB2 agonist: JWH-133 in mice using passive avoidance (PA) test to measure memory-related responses, elevated plus maze (EPM) test to measure anxiety-related behavior and forced swimming test (FST) to measure depression-related responses. Total antioxidant capacity (TAC) and lipids peroxidation level, expressed as malondialdehyde (MDA) concentration, were measured in homogenates of brain. Our findings revealed that a single injection of JWH-133 improved memory in PA, had an anxiogenic effects in EPM, antidepressant effects in FST and slightly increased total antioxidant capacity but did not affect lipids peroxidation level in brain. CB2 ligands could become a new pharmacological alternative in treatment of AD which is associated not only with emotional-related disorders but also with oxidative stress.

8

Hyperoside isolated from Impatiens glandulifera Royle alleviates depressive and anxiety-like responses in a mouse model of posttraumatic stress disorder

61%

Orzelska-Gorka J. , Szewczyk K. , Kedzierska E. , Glowacka E. , Kruk-Slomka M. , Biala G.

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nr Suppl.1

EN

INTRODUCTION: Posttraumatic stress disorder (PTSD) is a chronic and prevalent psychiatric condition that may develop following exposure to traumatic events. Depressive symptoms and anxiety belong to the most frequent symptoms observed in PTSD patients. Less than 30% of PTSD patients achieve full remission with the use of available drugs. For this purpose, there is a clear need to develop more efficient and safer drugs as alternative and/or complimentary therapy for PTSD. Hyperoside (HYP) is one of the polyphenols found in Impatiens glandulifera. Our previous experiments showed that HYP exerted antidepressant effects, both after acute and chronic (14 days) treatment in mice in the forced swimming test (FST; data not published). AIM(S): The present study aimed to investigate the effect of HYP on the behavioural impairments (depression and anxiety) induced by a mouse single prolonged stress (mSPS) – a rodent model of PTSD. METHOD(S): mSPS protocol: mice were exposed to a series of short stressors. In particular, they were restrained for 2 h in a Plexiglas tubes (50 ml), placed in glass beakers and immersed in water (23‑25°C) for a group swim (10 min). Then, they were exposed to a beaker of soiled bedding taken from cages of rats (15 min), and at the end, they were exposed to anhydrous diethyl ether until they lost consciousness (approx. 2 – 3 min). Seven days after exposure to SPS, the administration of substances was started (during next 14 days). Then, animals were subjected to behavioural tests, including the elevated plus-maze test (EPM), measurement of locomotion, and FST. RESULTS: Mice given chronically HYP (3.75 and 7.5 mg/kg) after exposure to mSPS exhibited a reduction of immobility time in FST, and more open arm entries and longer open arms duration in EPM without affecting locomotor activity as compared to control‑mSPS group. CONCLUSIONS: In summary, our results suggested the potential of HYP in alleviating the mSPS-induced depressive and anxiety‑like responses.