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Mariaelvina Sala

Publications and source records attributed to Mariaelvina Sala.

11 recordsLinked to original sources
PubMed2007

Hallucinatory and rewarding effect of salvinorin A in zebrafish: kappa-opioid and CB1-cannabinoid receptor involvement.

RATIONALE: The hallucinatory effect and potential abuse of salvinorin A, the major ingredient of Salvia divinorum, has not been documented in animals. OBJECTIVE: The effects of salvinorin A on the zebrafish (Danio rerio) model, through its swimming behavior and conditioned place preference (CPP) task, was studied. MATERIALS AND METHODS: Swimming activity was determined in a squared observational chamber after an i.m. treatment of salvinorin A (0.1-10 microg/kg). For the CPP test, zebrafish were given salvinorin A (0.2 and 1 microg/kg) or vehicle and evaluated in a two-compartment chamber. RESULTS: Salvinorin A (0.1 and 0.2 microg/kg) induced accelerated swimming behavior in comparison with vehicle, whereas a "trance-like" effect, at doses as 5 and 10 microg/kg, was obtained. Pretreatment with the kappa-opioid antagonist, nor-binaltorphimine (nor-BNI; 10 mg/kg) and the cannabinoid type 1 (CB(1)) antagonist, rimonabant (1 mg/kg), blocked salvinorin A-induced both stimulating and depressive effects obtained at a dose of 0.2 and 10 microg/kg, respectively. In the CPP test, salvinorin A (0.2 and 0.5 microg/kg) produced an increase in the time spent in the drug-associated compartment. A dose of 1 microg/kg produced no effect, whereas a dose of 80 microg/kg induced aversion. Pretreatment with nor-BNI or rimonabant fully reversed the reinforcing properties of salvinorin A (0.5 microg/kg). CONCLUSIONS: Taken together, these results indicate that salvinorin A, as is sometimes reported in humans, exhibits rewarding effects, independently from its motor activity, suggesting the usefulness of the zebrafish model to study addictive behavior. These effects appear mediated by activation of both kappa-opioid and cannabinoid CB(1) receptors.

Animals↗
PubMed2006

5-HT1A receptors are involved in the anxiolytic effect of Delta9-tetrahydrocannabinol and AM 404, the anandamide transport inhibitor, in Sprague-Dawley rats.

The mechanism mediating the effects of cannabinoids on anxiety-related responses appear to involve cannabinoid CB1 and non-CB1 receptors. However, other neurotransmitters may play a role in such effect. This study shows evidence of an interaction between endocannabinoid system and serotonin (5-HT), 1A receptor subtype on anxiety-like behavior in Sprague-Dawley rats. The exogenous cannabinoid agonist, Delta9-tetrahydrocannabinol (THC), and N-(4-hydroxyphenyl)-arachidonylamide, the anandamide transporter inhibitor (AM 404) were evaluated in the elevated plus maze test. THC (0.075-0.75 mg/kg i.p.), given 30 min and AM 404 (0.75-1.25 mg/kg i. p.), given 60 min before the test, exhibited a dose-response anxiolytic effect evaluated in terms of increase in the percentage of total entries and time spent in the open and decrease of total entries and time spent in the closed arms. The anxiolytic effect obtained with the maximal active dose of both THC (0.75 mg/kg) and AM 404 (1.25 mg/kg) was blocked by the 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide dihydro chloride (WAY-100635 (300 microg/kg, s.c.), given 30 min before THC or 15 min before AM 404. The combination of an ineffective dose of THC (0.015 mg/kg) or AM 404 (0.015 mg/kg) on anxiety-related responses with an ineffective dose of the 5HT(1A) receptor agonist, 8-Hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT) (7.5 microg/kg, i.p.), led to a synergistic effect. No interference with spontaneous motor activity, evaluated in an activity cage for 5 min, in rats given the drugs alone or in combination, was found. These data suggest that the anxiolytic effect produced by endo- and eso-cannabinoids is modulated by 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2006

Vanilloid VR1 receptor is involved in rimonabant-induced neuroprotection.

Recently, a potential neuroprotective effect of rimonabant, independent of the CB1 receptor interaction, has been proposed. In the present study, the role of transient receptor potential channel vanilloid subfamily member 1, named VR1, on neuroprotective effect of rimonabant, on global cerebral ischemia in gerbils, was investigated. Rimonabant (0.05-3 mg kg-1), given i.p. 5 min after recirculation, dose dependently antagonized the ischemia-induced decrease in electroencephalographic (EEG) total spectral power and restored relative frequency band distribution 7 days after ischemia. Rimonabant (0.125-0.5 mg kg-1) fully prevented ischemia-induced hyperlocomotion 1 day after ischemia and memory impairment evaluated in a passive avoidance task, 3 days after ischemia. At 7 days after ischemia, the survival of pyramidal cells, in the CA1 subfield, was respectively 91 and 96%, in the animals given rimonabant 0.25 and 0.5 mg kg-1, compared to the vehicle group. Higher doses were not protective. The protection induced by rimonabant followed a bell-shaped curve, the maximal active doses being 0.25 and 0.5 mg kg-1. Capsazepine (0.01 mg kg-1), a selective VR1 vanilloid receptor antagonist, completely reversed rimonabant-induced neuroprotective effects against EEG flattening, memory impairment and CA1 hippocampal neuronal loss. These findings suggest that VR1 vanilloid receptors are involved in rimonabant's neuroprotection even if other mechanisms can contribute to this effect.

Animals↗
PubMed2005

Capsaicin exhibits neuroprotective effects in a model of transient global cerebral ischemia in Mongolian gerbils.

1. Capsaicin, the irritant principle of hot peppers, is a vanilloid agonist known to activate the transient receptor potential channel vanilloid subfamily member 1 (VR1), recently reported to be involved in neurodegeneration. The present study investigated the role of VR1 in a model of global cerebral ischemia in gerbils. 2. Over the dose range tested, capsaicin (0.01, 0.025, 0.05, 0.2 and 0.6 mg kg(-1)), given 5 min after recirculation, dose-dependently antagonized the ischemia-induced electroencephalographic total spectral power decrease and restored relative frequency band distribution evaluated 7 days after ischemia. 3. Capsaicin, at all tested doses, fully prevented ischemia-induced hyperlocomotion evaluated 1 day after ischemia. 4. Capsaicin dose-dependently antagonized ischemia-induced memory impairment evaluated in a passive avoidance task, 3 days after ischemia. 5. Capsaicin showed a dose-dependent hypothermic effect evaluated for 2 h after recirculation. 6. At 7 days after ischemia, a progressive survival of pyramidal cells in the CA1 subfield in capsaicin-treated gerbils, with a maximum of 80%, at a dose of 0.2 mg kg(-1), was obtained. 7. The selective VR1 antagonist, capsazepine (0.01 mg kg(-1)), reversed capsaicin-induced protective effects, in a competitive manner. 8. These results suggest that the neuroprotective effect of capsaicin may be attributable, at least in part, to VR1 desensitization and provide a valuable target for development of interventional pharmacological strategies.

Animals↗
PubMed2004

Delta9-tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats.

On the basis of contradictory findings on the rewarding effects of Delta9-tetrahydrocannabinol (Delta9-THC) in laboratory animals, the effect of the compound on conditioned place preference and intracerebroventricular (i.c.v.) self-administration in a free-choice procedure, using a wide range of doses (0.015-6 mg/kg for conditioned place preference test and 0.01-1 microg/2 microl/infusion for i.c.v. self-administration), was studied in Wistar rats. The present results showed that Delta9-THC induced reward in both tests, but only at the lowest tested doses (0.075-0.75 mg/kg i.p. for conditioned place preference test and 0.01-0.02 microg/infusion for i.c.v. self-administration). This effect was fully antagonised by i.p. pretreatment with the cannabinoid CB1 receptor antagonist, SR 141716A [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichlorophenyl)-4 methyl pyrazole 3-carboxamide] (0.25-1 mg/kg), and the opiate receptor antagonist, naloxone (0.5-2 mg/kg), suggesting the involvement of both endocannabinoid and opioid systems. In conclusion, these findings demonstrate, for the first time, that low doses of Delta9-THC can act as an effective reinforcer in Wistar rats providing a reliable animal model of human marijuana abuse.

Animals↗
PubMed2004

Cognitive function in young and adult IL (interleukin)-6 deficient mice.

Interleukin-6 (IL-6) is a cytokine shown to affect brain function and to be involved in pathological neurodegenerative disorders such as Alzheimer's disease (AD). In the present study we investigated the cognitive function in transgenic mice not expressing IL-6 (IL-6 KO) and in wild type (WT) genotype at 4 and 12 months of age, using a passive avoidance and an eight-arm radial maze tasks. Motor function was quantified using an Animex apparatus. Hippocampal choline acetyltransferase (ChAT) activity was evaluated in both genotypes. No difference was observed in both genotypes for spontaneous motor activity. The mean latency (s) to re-enter the shock box, was similar in both young mutant and WT mice. However, a decreased sensitivity (50%) to scopolamine (1 mg/kg) in mutant compared to WT mice, was obtained. IL-6 KO mice exhibited a facilitation of radial maze learning over 30 days, in terms of a lower number of working memory errors and a higher percentage of animals reaching the criterion as compared with WT genotype tested at both ages. Furthermore, mutant mice, at the age of 12 months, showed a faster acquisition (22 days versus 30 days to reach the criterion). The pattern of arm entry exhibited by IL-6 KO mice showed a robust tendency to enter an adjacent arm at both ages, while WT only at the age of 4 months. ChAT activity was inversely correlated with memory performance. These findings suggest a possible involvement of IL-6 on memory processes, even if the mechanism remains still unclear.

Age Factors↗
PubMed2004

Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain.

In many species, the Sox2 transcription factor is a marker of the nervous system from the beginning of its development, and we have previously shown that Sox2 is expressed in embryonic neural stem cells. It is also expressed in, and is essential for, totipotent inner cell mass stem cells and other multipotent cell lineages, and its ablation causes early embryonic lethality. To investigate the role of Sox2 in the nervous system, we generated different mouse mutant alleles: a null allele (Sox2beta-geo 'knock-in'), and a regulatory mutant allele (Sox2DeltaENH), in which a neural cell-specific enhancer is deleted. Sox2 is expressed in embryonic early neural precursors of the ventricular zone and, in the adult, in ependyma (a descendant of the ventricular zone). It is also expressed in the vast majority of dividing precursors in the neurogenic regions, and in a small proportion of differentiated neurones, particularly in the thalamus, striatum and septum. Compound Sox2(beta-geo/DeltaENH) heterozygotes show important cerebral malformations, with parenchymal loss and ventricle enlargement, and L-dopa-rescuable circling behaviour and epilepsy. We observed striking abnormalities in neurones; degeneration and cytoplasmic protein aggregates, a feature common to diverse human neurodegenerative diseases, are observed in thalamus, striatum and septum. Furthermore, ependymal cells show ciliary loss and pathological lipid inclusions. Finally, precursor cell proliferation and the generation of new neurones in adult neurogenic regions are greatly decreased, and GFAP/nestin-positive hippocampal cells, which include the earliest neurogenic precursors, are strikingly diminished. These findings highlight a crucial and unexpected role for Sox2 in the maintenance of neurones in selected brain areas, and suggest a contribution of neural cell proliferative defects to the pathological phenotype.

Alleles↗
PubMed2003

Post-ischemic treatment with cannabidiol prevents electroencephalographic flattening, hyperlocomotion and neuronal injury in gerbils.

The potential activity of cannabidiol, a non-psychoactive constituent of marijuana, in preventing damage caused by cerebral ischemia was studied. Cannabidiol (1.25-20 mg/kg) was given 5 min after 10 min bilateral carotid occlusion in freely-moving awake gerbils. Seven days after ischemia, it antagonized the electroencephalographic flattening of total spectral power, with a dose-dependent bell-shaped curve; the neuroprotective effect was greatest with 5 mg/kg. One day after ischemia cannabidiol completely antagonized ischemia-induced hyperlocomotion, at all doses. Rectal temperature did not change during the first hour after occlusion. Histological examination showed complete survival of CA1 neurons in cannabidiol-treated gerbils. These findings suggest a potential therapeutic role of cannabidiol in cerebral ischemia, though the clear mechanism of action remains to be elucidated.

Animals↗
PubMed2002

3,4 methylenedioxymethamphetamine (ecstasy) impairs eight-arm radial maze performance and arm entry pattern in rats.

The recreational use of 3,4 methylenedioxymethamphetamine (ecstasy) in humans has been associated with memory impairment. The present study examined whether ecstasy impairs short- and long-term working memory and the pattern of arm entries in rats tested in the 8-arm radial maze with a 2-hr delay. After completing the training session, the rats were given a single dose of ecstasy (1, 2, or 3 mg/kg ip) 20 min before the test. The highest dose slightly affected short-term working memory. Under conditions of delay, there was a progressive deficit in long-term working memory, starting from 1 mg/kg. Under both test conditions, 2 and 3 mg/kg flattened the pattern of arm entry. None of the doses caused hyperlocomotion or stereotypy in the radial maze. These findings suggest that acute ecstasy mainly affects the long-term components of working memory and disrupts the pattern of arm entry in a way similar to serotonergic agents.

Animals↗
PubMed2002

Role of the endocannabinoid system in MDMA intracerebral self-administration in rats.

I.c.v. self-administration of MDMA (0.01-2 micro g per infusion), alone and in combination with CP 55,940 (0.4 micro g infusion(-1)), was studied on an operant responding procedure. On the basis of individual preference for one of two levers, developed during training, rats were allowed to self-administer vehicle from the preferred lever and MDMA from the other. Pressings on the MDMA associated-lever, except for the maximal unit dose, progressively increased. The combination of CP 55,940 with MDMA (1 micro g infusion(-1)) reduced the number of drug-associated lever pressings compared to the single drugs. Pre-treatment with SR 141716A (0.5 mg kg(-1) i.p.), 15 min before each daily session, significantly increased MDMA self-administration. These findings suggest that MDMA self-administration is under endogenous tonic control by the endocannabinoid system.

Animals↗