21 research outputs found
Adult hippocampal neurogenesis as a target for cocaine addiction: a review of recent developments
No full textAuthor manuscriptBasic research in rodents has shown that adult hippocampal neurogenesis (AHN) plays a key role in neuropsychiatric disorders that compromise hippocampal functioning. The discovery that dependence-inducing drugs regulate AHN has led to escalating interest in the potential involvement of AHN in drug addiction over the last decade, with cocaine being one of the most frequently investigated drugs. This review argues that, unlike other drugs of abuse, preclinical evidence does not, overall, support that cocaine induces a marked or persistent impairment in AHN. Nevertheless, experimental reduction of AHN consistently exacerbates vulnerability to cocaine. Interestingly, preliminary evidence suggests that, on the contrary, increasing AHN might help both to prevent and treat addiction.This study was funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO, Agencia Estatal de Investigación) cofounded by the European Regional Development Fund -AEI/FEDER, UE- (‘Jóvenes Investigadores grant’ PSI2015-73156-JIN to E.C.O.; and PSI2017-82604R to L.J.S.)
Validation of the Simulator for Testing and Rating Endovascular SkillS (STRESS)-machine in a setting of competence testing.
No full textItem does not contain fulltextAIM: Endovascular skills are an integral part of modern-day vascular surgery. The STRESS machine has been developed to test these skills in vascular surgeons. This study aims to define an optimal pass/fail cutoff value for the STRESS test score. METHODS: The STRESS machine consists of a dry glass model of the abdominal aorta and its tributaries with various stenotic lesions, elongations, and tortuosities. A camera and computer software are used to simulate plain fluoroscopy-mode. The test subjects are given two assignments after which two reviewers use a combination of the ICEPS and MRS to produce the final total score; 43 subjects were tested. According to previous endovascular experience, subjects were classified into four groups: novice-low (no experience, less than 11 performed procedures, less than 50 assisted procedures), novice-high (11-25 performed procedures, more than 50 assisted procedures), intermediate (1-10 performed and >11-25 assisted procedures, 11-25 performed and >1-10 assisted procedures or 25-50 performed procedures) and advanced (more than 50 performed procedures). RESULTS: Test-score and noted experience showed a correlation of 0.794. All intermediate and advanced test subjects scored more than 50 points compared to 4 out of 15 novices. CONCLUSION: We demonstrated that it is possible to determine an optimal cut-off value for competence testing with the STRESS machine.01 april 201
Neuroplastic and cognitive impairment in substance use disorders: a therapeutic potential of cognitive stimulation
No full textAuthor manuscriptDrug addiction is a chronic and relapsing disorder in which repeated drug exposure compromises brain neuroplasticity. Brain areas normally involved in learning and goal- directed behaviors become corrupted, which may lead to cognitive deficits that coexist with other addiction symptoms and predict a worse treatment outcome. New learning experiences that are not motivated by drugs may improve both cognitive deficits and drug-induced symptoms by promoting adaptive neuroplastic changes that could alleviate or reverse those involved in addiction. The present review will focus on whether potentiating healthy cognitive function, either by formal cognitive training or non-drug related environmental experiences, could exert beneficial effects in the therapeutics of addiction. Although additional studies are needed, the available clinical and preclinical evidence suggests that cognitive stimulation may provide a valuable adjuvant intervention in drug addiction.This study was funded by grants from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación) co-founded by the European Research Development Fund-AEI/FEDER, UE- (PSI2015-73156-JIN to E.C.O.; PSI2017-82604R to L.J.S.), Red de
Trastornos Adictivos (RD16/0017/0001 to F.R.F.), Plan Nacional sobre Drogas, Ministerio de Sanidad, Servicios Sociales e Igualdad (PNSD2015/047 to J.S.) and the University of Málaga (Plan Propio 2017 – ‘Ayudas para proyectos dirigidos por jóvenes investigadores’, PPIT.UMA.B1.2017/38 to P.S.P).
Author P.S.P. holds a ‘Juan de la Cierva-formación’ grant from the Spanish Ministry of Economy, Industry and Competitiveness (code: FJCI-2015-23925). Author D.L.G.M. holds a ‘FPU’ grant from the Spanish Ministry of Education, Culture and Sports (code: FPU13/04819). Authors J.S., A.S. and F.J.P. hold ‘Miguel Servet’ grants (codes: CPII17/00024, CP14/00173 and CP14/00212, respectively) from the National System of Health-Instituto de Salud Carlos- III co-funded by FEDER, UE. Author E.C.O. holds a ‘Jóvenes Investigadores’ grant (code: PSI2015-73156-JIN) from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación) co-funded by FEDER, UE
Galanin n-terminal fragment (1-15) induces an anxiety- and depressive-like behaviours in the light/dark and tail suspension tests
No full textGalanin N-terminal fragment (1-15) [Gal(1-15)] is involved in mood regulation. We have shown that intracerebroventricular (icv) administration of Gal(1-15) produces a depressive-like behaviour in the forced swim test (FST) and an anxiety-like behaviour in the open field test (OF) in rats. In this work we analyze the effect of Gal(1-15) in two more behavioural tests, the tail suspension test (TLT) and the light/dark test.
In light/dark test we studied during 5 min the latency time for entering the dark box, time spent in the light compartiment, and the latency time for re-entering the light box as parameters indicators of anxiety-like behaviour. In TLT total immobility time was analyzed during 6 min test as parameter indicator of depressive-like behaviour.
Groups of rats (n=5-8) were injected icv with Gal(1-15) 3nmol, a dose effective in FST and OF, or artificial cerebrospinal fluid 15 minutes before the test. Behavioural assessment were conducted with at least one week between tests. Student’s t-test was used for comparation between experimental groups.
In the light/dark test Gal(1-15) 3nmol significantly reduced the time spent in the light compartiment by 52% (p<0.05) and the latency time for entering the dark box by 65% (p<0.05). An increased in the latency time for re-entering the light box was also observed (p<0.05). This pattern of results reflects an anxiogenic-like effects of Gal(1-15) in this test.
In the TST, the administration of Gal(1-15) 3nmol significantly increased rat immobility by 16% (p<0.05) indicating a depressive-like effect.
These results confirm the depressive- and anxiety-like effects of Gal(1-15) in rats. Future therapeutic strategies based on these results could be developed for depression and anxiety disorders.
This work has been supported by the Junta de Andalucia CVI6476 and Spanish Ministry of Economy and Competitiveness (PSI2013-44901-P to L.J.S)Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work has been supported by the Junta de Andalucia CVI6476 and Spanish Ministry of Economy and Competitiveness (PSI2013-44901-P to L.J.S)Author A.F-B. holds a ‘FPI’ grant from the Spanish Ministry of Economy and Competitiviness (grant number BES-2014-068426)
Where to place the rewards? Exploration bias in mice influences performance in the classic hole-board spatial memory test
No full textAuthor manuscriptThe classic hole-board paradigm (a square arena with 16 holes arranged equidistantly in a 4x4 pattern) assesses both exploration and spatial memory in rodents. For spatial memory training, food rewards are hidden in a fixed set of holes. The animal must not visit (i.e. nose-poke) the holes that are never baited (reference memory; RM) nor re-visit a baited hole within a session (working memory; WM). However, previous exploratory bias may affect performance during reward searching. During habituation sessions with either all holes rewarded or all holes empty, mice intrinsically preferred poking peripheral holes (especially those located in the maze’s corners) over centre holes. During spatial memory training, mice progressively shifted their hole pokes and staying time to the central area that contained hidden rewards, while mice exposed to the empty apparatus still preferred the periphery. A group of pseudotrained mice, for whom rewards were located randomly throughout the maze, also increased their central preference. Furthermore, reward location influenced memory measures. Most repeated pokes (WM-errors) were scored in the locations that were most intrinsically appealing to mice (i.e. the corner and wall baited holes), supporting a strong influence of previous exploratory bias. Regarding RM, finding rewards located in the centre holes, which were initially less preferred, entailed more difficulty and required more trials to learn. This outcome was confirmed by a second experiment that varied the pattern of rewarded holes, as well as the starting positions. Therefore, reward location is a relevant aspect to consider when designing a hole-board memory task.This study was funded by grants from the Spanish Ministry of Economy and
Competitiveness (MINECO, Agencia Estatal de Investigación) cofounded by the
European Research Development Fund -AEI/FEDER, UE- (PSI2015-73156-JIN to
E.C.O.; PSI2017-82604R to L.J.S.) and from University of Malaga (Plan Propio 2017 –
‘Ayudas para proyectos dirigidos por jóvenes investigadores’, PPIT.UMA.B1.2017/38 to
P.S.P).
Author P.S.P. holds a ‘Juan de la Cierva-formación’ grant from the Spanish Ministry of
Economy, Industry and Competitiveness (code: FJCI-2015-23925). Author M.M.P. holds
Predoctoral contract from University of Malaga (Plan Propio 2017). Author F.A.G holds
Young researchers contract from the University of Malaga co-funded by the Regional
Government of Andalusia and the European Social Fund. Author E.C.O holds a ‘Jóvenes
Investigadores’ grant (code: PSI2015-73156-JIN) from MINECO-AEI/FEDER, UE
Highlighting the role of cognitive and brain reserve in the substance use disorder field
No full textAuthor manuscriptBackground: Cognitive reserve (CR) refers to the ability of an individual to cope with brain pathology remaining free of cognitive symptoms. This protective factor has been related to compensatory and more efficient brain mechanisms involved in resisting brain damage. For its part, Brain reserve (BR) refers to individual differences in the structural properties of the brain which could also make us more resilient to suffer from neurodegenerative and mental diseases. Objective: This review summarizes how this construct, mainly mediated by educational level, occupational attainment, physical and mental activity, as well as successful social relationships, has gained scientific attention in the last years with regard to diseases, such as neurodegenerative diseases, stroke or traumatic brain injury. Nevertheless, although CR has been studied in a large number of disorders, few researches have addressed the role of this concept in drug addiction. Methods: We provide a selective overview of recent literature about the role of CR and BR in preventing substance use onset. Likewise, we will also discuss how variables involved in CR (healthy leisure, social support or job- related activities, among others) could be trained and included as complementary activities of substance use disorder treatments. Results: Evidence about this topic suggests a preventive role of CR and BR on drug use onset and when drug addiction is established, these factors led to less severe addiction-related problems, as well as better treatment outcomes. Conclusion: CR and BR are variables not taken yet into account in drug addiction. However, they could give us a valuable information about people at risk, as well as patient’s prognosis.This study was funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO, Agencia Estatal de Investigación) cofounded by the European Research Development Fund -AEI/FEDER, UE- (PSI2015-73156-JIN to E.C.O.; PSI2017-82604R to L.J.S.) and from University of Malaga (Plan Propio 2017 – ‘Ayudas para proyectos dirigidos por jóvenes investigadores’, PPIT.UMA.B1.2017/38 to P.S.P.). Author D.L.G.M. holds a ‘FPU’ grant from the Spanish Ministry of Education, Culture and Sports (code: FPU13/04819). Author E.C.O. holds a ‘Jóvenes Investigadores’ grant (code: PSI2015-73156-JIN) from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación) co-funded by FEDER, UE. Author P.S.P. holds a ‘Juan de la Cierva-formación’ grant from the Spanish Ministry of Economy, Industry and Competitiveness (code: FJCI-2015-23925)
Effects of galanin n-terminal fragment (1-15) in the light/dark and tail suspension tests
No full textGalanin N-terminal fragment (1-15) [Gal(1-15)] is involved in mood regulation. The intracerebroventricular (icv) administration of Gal(1-15) produces a depressive-like behaviour in the forced swim test (FST) and an anxiety-like behaviour in the open field test (OF) in rats. In this work we analyze the effect of Gal(1-15) in two more behavioural tests, the tail suspension test (TLT) and the light/dark test.
Gal(1-15) (3nmol), effective dose in FST and OF, or artificial cerebrospinal were injected in animals (n=5-8) 15 minutes before the test. Behavioural assessment were conducted with at least one week between tests. Student’s t-test was used for comparision between experimental groups.
In the light/dark test we analyzed during 5 min three parametres as indicators of anxiety-like behaviour. Gal(1-15) significantly reduced the time spent in the light compartiment by 52% (p<0.05) and the latency time for entering the dark box by 65% (p<0.05). An increased in the latency time for re-entering the light box was also observed (p<0.05).
In the TST, total immobility time was analyzed during 6 min test as parameter indicator of depressive-like behaviour. Gal(1-15) significantly increased rat immobility by 16% (p<0.05).
Our results describe that Gal(1-15) exerts strong depressive- and anxiety-like effects in these tests, indicating a potential role of Gal(1-15) in mood disorders. These results may give the basis for the development of novel therapeutic drugs targeting Gal(1-15) for depression and anxiety.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Junta de Andalucia CVI6476 // Spanish Ministry of Economy and Competitiveness (PSI2013-44901-P to L.J.S). Author A.F-B. holds a ‘FPI’ grant from the Spanish Ministry of Economy and Competitiviness (grant number: BES-2014-068426)
Persistent changes in exploration and hyperactivity coexist with cognitive impairment in mice withdrawn from chronic cocaine
No full textRepeated cocaine exposure induces lasting neurobehavioral adaptations such as cognitive decline in animal
models. However, persistent changes in spontaneous –unconditioned- motor and exploratory responses are
scarcely reported. In this study, mice were administered with cocaine (20 mg/kg/day) or vehicle for 12
consecutive days. After 24 days of drug abstinence, a behavioral assessment was carried out in drug-free conditions
and in unfamiliar environments (i.e. no cocaine-associated cues were presented). The cocaine-withdrawn
mice showed cognitive deficits in spontaneous alternation behavior and place recognition memory. Importantly,
they also displayed hyperlocomotion, increased rearing activity and altered exploratory patterns in different
tasks. In the forced swimming test, they were more active (struggled/climbed more) when trying to escape from
the water albeit showing normal immobility behavior. In conclusion, in addition to cognitive deficits, chronic
cocaine in rodents may induce long-lasting alterations in exploratory activity and psychomotor activation that
are triggered even in absence of drug-related stimuli.This study was funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO, Agencia Estatal de Investigación –AEI-) cofounded by the European Regional Development Fund-FEDER, UE- (PSI2015–73,156-JIN to E.C–O.; PSI2017–82604R to L.J.S.), RETICS Red de Trastornos Adictivos (ERDF-EU; RD16/0017/0001 to F.R.F.) and University of Málaga (B4: ‘Ayudas para Proyectos Puente’to E.C–O). Funding for open access charge: Universidad de Málaga /CBUA.
Authors M.C.M-P., F. A-G. and S. G-R. hold predoctoral grants from the Spanish Ministry of Science, Innovation and Universities (FPU17/00276 to M.C.M-P.; PRE2018–085673 to F.A-G.; and FPU18/00941 to S.G-R.). Author D.L.G.M. holds a postdoctoral grant from University of Málaga (A.3. Plan Propio de Investigación y Transferencia Universidad de Málaga)
The limbic brain under stress: a role for the LPA1 receptor
No full textAdverse events can impact brain structure and function and are considered primary sources of risk for depression, anxiety, and other psychiatric disorders. In this sense, the neurobiological circuitry in charge of dealing with stressors has been widely studied in animal models. Our group has demonstrated a role for lysophosphatidic acid (LPA) through the LPA1-receptor in controlling anxious and depressive states, owing to aggravation of the detrimental consequences of stress in the brain. Indeed, our group has recently proposed the variant maLPA1-null mice, i.e. mice lacking the LPA1 receptor, as an endophenotype for anxious depression. In addition, we have previously reported hyperactivation of key stress-related brain areas after stress, such as basolateral amygdala.
Here, we seek to further examine the engagement of the LPA1 receptor in the regulation of the limbic circuit following an acute stressor, tail suspension test, in wildtype and knockout animals. To that end, c-Fos expression was evaluated as a measure of functional activity in both basal and stress conditions, followed by interregional correlation matrices to establish the brain map of functional activation. Additionally, we observed whether one single dose of the antidepressant treatment with desipramine is able to normalize the functional brain map.
Results revealed that the absence of the LPA1 receptor induce an anomalous pattern of brain functional activity after TST, which was reverted by desipramine administration.These results provide further insight to the involvement of the LPA1 receptor in stress regulation and shed light on divergent brain pathways under normal and vulnerability conditions that can be implicated in depressive symptoms. Finally, how this pattern might be reverted by antidepressant treatment can be useful for developing new pharmaceutical targets regarding the LPA1 receptor.Funding: Andalusian Ministry of Economy, Innovation, Science and Employment (SEJ1863 to C.P) and of Health (Nicolas Monardes programme, to G.E-T); the Spanish Ministry of Economy and Competitiveness (PSI2013-44901-P to L.J.S. and C.P.). Author R.D. M-F holds a Grant of the Spanish Ministry of Education, Culture and Sports (FPU14/01610). Author S.T. holds a Grant of the Andalusian Ministry of Economy, Innovation, Science and Employment (FPDI 2014). I Plan Propio de Investigación y Transferencia, Universidad de Málaga. Campus de Excelencia. Andalucía Tech
Reduction of adult hippocampal neurogenesis modifies brain functional connectivity and enhances cocaine-seeking in mice
No full textRecently, adult hippocampal neurogenesis has been proposed as a putative neuroplastic mechanism involved in those behavioural processes. In this work, we studied the effect of the inhibition of adult hippocampal neurogenesis using the DNA alkylating agent temozolomide (TMZ), in cocaine-induced conditioned place preference (CPP) behaviour. In a first experiment, we investigated both CPP acquisition/expression and the functional brain circuits underlying CPP expression in control and neurogenesis-reduced conditions by analysing c-Fos immunoreactivity (c-Fos IR) in hippocampal and extrahippocampal addiction-related areas. A second experiment was designed to study the involvement of adult-born neurons in the extinction and cocaine-induced reinstatement of drug-seeking in the CPP model. We performed two independent studies where adult hippocampal neurogenesis was inhibited either before or after the CPP was acquired. Our results showed that TMZ treatment had no effect on the acquisition of the cocaine-induced CPP, but c-Fos IR associated to the test trial (CPP expression) revealed an increased activity in some of the analysed brain areas in the CPP-TMZ mice. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain network associated with CPP expression. However, mice with reduced neurogenesis showed an alternative brain circuit. The results of the second experiment revealed that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug seeking behaviour. However, when neurogenesis was inhibited after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that the role of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition.Universidad de Málaga. Andalucía Tech, Campus de Excelencia Internacional. Spanish Ministry of Economy and Competitiveness (PSI2013-44901-P to L.J.S.; Subprograma RETICS Red de Trastornos Adictivos RD12/0028/0001, to F.R.F.). Author E.C-O. holds a ‘Sara Borrell’ research contract from the Spanish Carlos III Health Institute, Spanish Ministry of Economy and Competitiviness (grant number CD12/00455). Author D.L.G-M. holds a ‘FPU’ grant from the Spanish Ministry of Education, Culture and Sports (grant number FPU13/04819)
