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Biomedical subjects

F Boix

Publications and source records attributed to F Boix.

At least 19 recordsLinked to original sources
PubMed1998

Chronic L-deprenyl treatment alters brain monoamine levels and reduces impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder.

Effects of chronic L-deprenyl administration on hyperactive behaviour and brain monoamine levels were studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. SHR were hyperactive, impulsive and had impaired sustained attention when tested with a multiple 2-min fixed interval (FI) 5-min extinction (EXT) schedule of reinforcement. Even low, 0.25 mg/kg, doses of chronically-administered L-deprenyl reduced the impulsiveness (bursts of responses with short interresponse times) of SHR, without altering the general hyperactivity or the impaired sustained attention. The drug had no effect on WKY behaviour. The levels of noradrenaline (NA), dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT) and their metabolites, measured in neostriatum, nucleus accumbens and frontal cortex, showed that L-deprenyl effectively inhibited monoamine oxidase (MAO) activity. These results suggest that impulsiveness is a behavioural component that may be operating independent of the other components, like hyperactivity and deficient sustained attention, and that can be reduced by chronic MAO-B inhibition with L-deprenyl in this strain of rats. The positive effect of L-deprenyl on impulsiveness is discussed as due either to normalization of an asymmetric dopaminergic activity in the nucleus accumbens, or to a restoration of normal DA function in the prefrontal cortex.

Animals↗
PubMed1997

Short term storage of samples containing monoamines: ascorbic acid and glutathione give better protection against degradation than perchloric acid.

In order to study the protection of monoamines from degradation during short-time storage, the effect of three different antioxidants on the degradation of dopamine, dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) was analyzed after 5 and 20 h. The results showed that dopamine was still quite stable after 20 h storage at room temperature, but that about 95% of 5-HIAA had disappeared. The best protection against degradation of all three substances was achieved when 15% v/v of a solution containing 1-2 mM ascorbic acid or 40 mM glutathione was added to the sample, resulting in near 100% protection after 20 h. Perchloric acid actually accelerated the degradation of 5-HIAA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats.

Adenosine is an inhibitory modulator in the mammalian brain with a possible role in sleep regulation, which is mainly indicated by pharmacological studies showing that adenosine or its analogs can induce sedation and sleep, whereas adenosine antagonists, like caffeine and theophylline, are potent behavioral and neuronal stimulants. In contrast to these pharmacological findings, data on endogenous adenosine in relation to sleep and waking are sparse. Therefore, we have now used in vivo microdialysis to investigate the extracellular levels of adenosine in the neostriatum and hippocampus of freely moving rats. Adenosine was monitored over a time course of 24 h, during which the animals were exposed to a 12 h day/night rhythm with lights-off from 19.00 to 07.00. In this lights-off period, i.e. the rats' active period, the maximal levels of neostriatal and hippocampal extracellular adenosine were higher than during the lights-on period. In contrast to the neostriatum, extracellular levels of hippocampal adenosine tended to increase towards the end of the lights-off period, reaching its maximal level at 07.00, and decreasing again within the following hour. The changes of hippocampal adenosine levels were related to behavior, since significant increases in "sleep-like" behavior, as well as decreases in overall movements and consummatory behavior, were observed when adenosine levels had reached their maxima in the hippocampus; no such relationship was found with respect to the neostriatum. These results are in keeping with a role of endogenous adenosine in the regulation of sleep and wakefulness, and point to a specific role of adenosine in the hippocampus. They also raise the possibility that adenosine may be involved in different behavioral processes dependent on the area of the brain, as well as the type of adenosine receptor involved. Finally, given the known evidence for neuroprotective actions of adenosine, its accumulation in the hippocampus as a function of behavioral activity may serve to prevent or repair the neural degenerative consequences of such activity. It is proposed that adenosine's sleep-promoting effects result from its signalling to cease behavioral activity in order to prevent excessive activity-related changes, and thus allow other restorative sleep-related processes to take over.

Adenosine↗
PubMed1995

Relationship between dopamine release in nucleus accumbens and place preference induced by substance P injected into the nucleus basalis magnocellularis region.

The activity of the neurotransmitter dopamine in the nucleus accumbens is considered to be an important element in the central processing of reinforcement. Unilateral administration of the neurokinin substance P into the area of the nucleus basalis magnocellularis of rats was found to be reinforcing, as assessed by the conditioned place preference paradigm. Simultaneous in vivo microdialysis showed that administration of substance P into the area of the nucleus basalis magnocellularis could increase extracellular concentrations of dopamine in the contralateral nucleus accumbens. Only those animals in which the administration of substance P induced this increase in dopamine levels acquired place preference. Furthermore, the changes in extracellular dopamine levels after substance P administration had a bimodal time course with an acute increase (to about 160% of baseline) during the first hour after injection, with a low (to 120-130%) and enduring increase occurring thereafter. Interestingly, during this second increase there were indications for positive correlations with the degree of place preference induced by substance P. Further positive correlations with place preference were found in the levels of the serotonergic metabolite 5-hydroxyindoleacetic acid. In contrast to dopamine, these were observed ipsi- and contralateral to the side of substance P administration. By combining the methods of in vivo microdialysis and conditioned place preference it was shown that the reinforcing effect induced by unilateral substance P injection in the nucleus basalis magnocellularis is related to dopaminergic (and possibly serotonergic) mechanisms in the nucleus accumbens.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Substance P decreases extracellular concentrations of acetylcholine in neostriatum and nucleus accumbens in vivo: possible relevance for the central processing of reward and aversion.

It has been shown that peripherally administered substance P has reinforcing effects and can promote functional recovery after unilateral partial lesion of the nigrostriatal system. Furthermore, peripheral injection of substance P induces an increase in extracellular striatal dopamine. To obtain further information about the central mechanisms of these properties we used the in vivo microdialysis technique to investigate changes in the extracellular concentrations of acetylcholine in neostriatum and nucleus accumbens after intraperitoneal (i.p.) administration of substance P or vehicle in freely moving rats. The i.p. administration of 50 micrograms/kg substance P induced a steady, long-lasting decrease in the extracellular concentrations of acetylcholine in neostriatum, while no changes were observed in the nucleus accumbens. In comparison, substance P in a dose of 250 micrograms/kg i.p. acutely decreased the extracellular levels of acetylcholine in both nuclei. Interestingly, after the administration of vehicle, an acute increase in acetylcholine levels was observed in the nucleus accumbens, but not in the neostriatum. This effect did not occur after the injection of substance P indicating that the neurokinin blocked the increase in acetylcholine levels induced by the vehicle injection. These effects of substance P on striatal acetylcholine are discussed with respect to their relationship with dopamine and endogenous opiates, and with respect to the functional role of substance P, such as in reward, aversion, motor activity, and functional recovery.

Acetylcholine↗
PubMed1994

Different effects of scopolamine on extracellular acetylcholine levels in neostriatum and nucleus accumbens measured in vivo: possible interaction with aversive stimulation.

The in vivo microdialysis technique was used to measure extracellular concentrations of acetylcholine (ACh) in the neostriatum (NS) and nucleus accumbens (NAc) of freely moving rats after intraperitoneal administration of the muscarinic receptor antagonist scopolamine (0.5 mg/kg) or vehicle. Simultaneously, behavior was monitored. The administration of scopolamine induced an increase in extracellular ACh levels in the NS, which reached a maximum of about 185% within one hour after injection and returned to baseline values about three hours after injection. In the NAc, an increase of similar time-course was observed; however, this increase reached a maximum of 250%, which was significantly higher than the one observed in NS. These changes in ACh levels were accompanied by enhanced locomotion, rearing and grooming; however, the behavioral changes were of shorter time-course than those of extracellular ACh. The injection of vehicle did not affect ACh levels in NS, but induced a significant increase (60%) in the NAc. The levels of behavioral activity after vehicle injection did not differ from pre-injection levels. These results suggest, that the cholinergic systems in the NAc and NS are differently affected by peripheral administration of both scopolamine and vehicle. The differential effects of scopolamine in NS and NAc could reflect pharmacodynamic differences between these two striatal brain areas, perhaps due to a higher density of cholinergic interneurons or muscarinic autoreceptors in the NAc in comparison to the NS. However, the increase of extracellular ACh observed after vehicle injection suggests that factors such as aversive stimulation through the injection procedure can increase ACh release in the NAc and that such a mechanism can interact within the action of scopolamine. Thus, the stronger action of scopolamine on extracellular ACh in the NAc might be an additive effect of the drug with that of the injection procedure.

Acetylcholine↗
PubMed1993

Behavioral indices of moderate nigro-striatal 6-hydroxydopamine lesion: a preclinical Parkinson's model.

Asymmetries in turning and scanning were investigated in rats with different degrees of neostriatal dopamine depletion after unilateral injections of 6-hydroxydopamine into the substantia nigra. Animals with severe lesions, i.e., residual dopamine levels of < 20%, spontaneously turned ipsiversive and showed more scanning behavior with the side ipsilateral to the lesion. These asymmetries were reversed by the dopamine receptor agonist apomorphine. Animals with less severe dopamine depletion, i.e., residual dopamine levels of 20-65%, did not show an asymmetry in spontaneous turning, but an ipsilateral asymmetry in scanning was still observed, indicating a greater sensitivity of this measure for moderate striatal dopamine depletions. Furthermore, in animals with residual dopamine levels of 45-65%, the dopamine receptor agonist apomorphine did not lead to a behavioral reversal as with severe lesions, but induced ipsilateral scanning and ipsiversive turning. These ipsiversive asymmetries are discussed in relation to asymmetries in self-regulatory mechanisms of the nigro-striatal dopamine system, such as dopamine autoreceptors controlling the release of this transmitter. Dopamine receptor-stimulated behavioral asymmetry in animals with moderate depletions of dopamine is suggested as a preclinical model to study mechanisms affected in the early state of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine activity.

There is ample evidence that the neurokinin substance P (SP) can have neurotrophic as well as memory-promoting effects. This paper outlines a recent series of experiments dealing with the effects of SP and its N- and C-terminal fragments on memory, reinforcement, and brain monoamine metabolism. It was shown that SP, when applied peripherally (IP), promotes memory (inhibitory avoidance learning) and is reinforcing (place preference task) at the same dose of 37 nmol/kg. Most important, however, is the finding that these effects seemed to be encoded by different SP sequences, since the N-terminal SP1-7 (185 nmol/kg) enhanced memory, whereas C-terminal hepta- and hexapeptide sequences of SP proved to be reinforcing in a dose equimolar to SP. These differential behavioral effects were paralleled by selective and site-specific changes in dopamine (DA) activity, as both SP and its C-, but not N-terminus, increased extracellular DA in the nucleus accumbens (NAc), but not in the neostriatum. The neurochemical changes lasted at least 2 h after injection. These results show that the reinforcing action of peripheral administered SP may be mediated by its C-terminal sequence, and that this effect could be related to DA activity in the NAc. Direct application of SP (0.74 pmol) into the region of the nucleus basalis magnocellularis (NBM) was also memory-promoting and reinforcing, and again, these effects were differentially produced by the N-terminus and C-terminus, supporting the proposed structure-activity relationship for SP's effects on memory and reinfrocement. These results may provide a hypothetical link between the memory-modulating and reinforcing effects of SP and the impairment in associative functioning accompanying certain neurodegenerative processes.

Amino Acid Sequence↗
PubMed1993

Peripherally administered substance P affects extracellular dopamine concentrations in the neostriatum but not in the nucleus accumbens under anesthesia.

The in situ microdialysis technique was used in urethane-anesthetized rats to monitor changes in the extracellular concentrations of dopamine and its metabolites in neostriatum and nucleus accumbens after the peripheral administration of substance P (50 or 250 micrograms/kg, IP). Four to five hours after urethane anesthesia a decrease of extracellular dopamine and its metabolites was observed which continued in the nucleus accumbens in the following 3 h. The administration of substance P induced a decrease in extracellular concentration of dopamine in neostriatum. This neurochemical change after substance P was not accompanied by parallel alterations in extracellular concentrations of dopamine metabolites. No effects of substance P were observed on dopamine or its metabolites in nucleus accumbens. These data are discussed in relation with the contrasting effects of substance P on awake rats and the possible changes in striatal dopamine activity induced by anesthetics.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

The C-terminal fragment of substance P enhances dopamine release in nucleus accumbens but not in neostriatum in freely moving rats.

The in vivo microdialysis technique was used to study the effects of carboxyl or amino terminal sequences of substance P on the extracellular concentrations of dopamine, its metabolites dihydroxyphenylacetic acid and homovanillic acid, as well as on 5-hydroxyindoleacetic acid, in neostriatum and nucleus accumbens of freely moving rats. The i.p. administration of 37 nmol/kg of the substance P C-terminal heptapeptide analog [pGlu5, MePhe8, Sar9]SP5-11 (DiMe-C7) caused an increase in extracellular dopamine concentrations in nucleus accumbens but not in neostriatum. The administration of the equimolar dose of the heptapeptide N-terminal fragment substance P 1-7 (SP1-7) did not have an effect in either structure. No changes were observed in the extracellular concentrations of the metabolites after the administration of either substance. These results are discussed with respect to the reinforcing effects of substance P and its C-terminal sequence, which may be mediated via dopamine release in the nucleus accumbens.

Animals↗
PubMed1992

Effects of substance P on extracellular dopamine in neostriatum and nucleus accumbens.

Microdialysis was used to monitor changes in dopamine release in the neostriatum and nucleus accumbens after peripheral administration of substance P in freely moving rats. Substance P in a dose of 50 micrograms/kg produced a steady moderate increase in dopamine levels in the neostriatum, which persisted for at least 5 h. In contrast, a dose of 250 micrograms/kg caused an acute increase in dopamine levels in the nucleus accumbens, which lasted about 2 h. These data suggest that the peripheral administration of substance P can influence dopamine release in mesolimbic and mesostriatal terminals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Lateralized changes in behavior and striatal dopamine release following unilateral tactile stimulation of the perioral region: a microdialysis study.

Intracranial microdialysis was used to measure dopamine (DA) release in the ventrolateral neostriatum of freely moving rats before and after unilateral tactile stimulation was applied to the orofacial region. Several behavioral parameters which have been linked to changes in nigrostriatal DA transmission (scanning, or snout contact with the walls of the observation chamber, turning and locomotion) were measured as well. Orofacial stimulation was followed by an asymmetrical increase in DA release with concentrations of transmitter higher in the neostriatum ipsilateral to the side of stimulation. Asymmetrical scanning behavior was observed during the time period when DA release was asymmetric, with rats favoring use of the side of the face contralateral to increased DA release. Increases in the DA metabolites DOPAC and HVA were found in the striatum ipsilateral to stimulation, but were delayed 40 min following the increase in DA.

Animals↗
PubMed1991

The early acquisition of two-way (shuttle-box) avoidance as an anxiety-mediated behavior: psychopharmacological validation.

Several lines of evidence have established that performance during the initial steps of acquisition on a shuttle-box avoidance task is an anxiety-mediated behavior (i.e., the differences between strains selectivity bred for emotionality; the effects of postnatal handling; the course of the corticosterone response and behavioral measures of fear during acquisition). The present study was carried out to add pharmacological evidence to that view by testing the action of anxiogenic and anxiolytic drugs. Single 40-trial sessions with mild shocks (0.4 mA-0.6 mA) were used. In the first experiments the action of sodium pentobarbital (1.25, 2.5 and 5 mg/kg) and three benzodiazepines (diazepam, 2 and 4 mg/kg; alprazolam, 1, 1.25 and 1.5 mg/kg and adinazolam, 1, 2, 4 and 6 mg/kg) were tested. The last two experiments tested a possible proanxiety action of Ro 15-4513 (2, 5 and 10 mg/kg) and FG 7142 (5, 10 and 15 mg/kg), two partial inverse agonists of benzodiazepine receptors, which previous data had suggested to be anxiogenic. The results showed that the measure of acquisition of a two-way active avoidance is a sensitive mean for detecting either anxiolytic or anxiogenic effects of drugs, independently of their effects on locomotor activity, thus suggesting that such test could be a valid model of anxiety in animals.

Animals↗
PubMed1991

Effects of different handling-stimulation procedures and benzodiazepines on two-way active avoidance acquisition in rats.

The acquisition of two-way active (shuttlebox) avoidance involves a conflict situation which can be used as an animal model of anxiety, since it is sensitive to manipulations of the animal's emotivity/reactivity. The results from the present study (experiment 1) add relevant support to that proposal, since diazepam (2 and 4 mg/kg) and the triazolobenzodiazepine alprazolam (1, 1.25 and 1.5 mg/kg) significantly improved avoidance performance in shuttlebox acquisition in rats in agreement with previous data. In another study (experiment 2), a mild stressful (10-day) handling procedure (i.e. handling which tends to increase the emotional reactivity of the animals, as showed in experiment 3) was found to affect such behaviour in an opposite direction to that of the two benzodiazepines. Conversely, when an habituating handling procedure (i.e. handling which leads to less reactive animals; experiment 3) was used, the acquisition of shuttlebox avoidance was improved (experiment 4). The results are discussed in relation with previous data showing that the particular parameters used in the exposure to stressful stimuli may lead to either sensitization or habituation of anxious responses.

Alprazolam↗
PubMed1990

Picrotoxin changes the effects of imipramine and desipramine in rats in the forced swimming test.

The aim was to find whether the chloride channel blocker, picrotoxin, at subconvulsant doses could affect the activity of imipramine or desipramine in the 'forced swimming' test with rats. It was found that picrotoxin enhanced the anti-immobility effects of imipramine and desipramine whereas open field activity remained unaffected or was even decreased by the same treatments. The results seem consistent with recent reports showing direct interactions between several antidepressant drugs and the GABAA receptor/benzodiazepine receptor/chloride ionophore complex (GABAA/benzodiazepine/Cl complex). The results also conform with the hypothesis that a reduction in the functionality of this complex could be related to the clinical effects of antidepressant drugs.

Animals↗
PubMed1990

Handling-habituation prevents the effects of diazepam and alprazolam on brain serotonin levels in rats.

In two different experiments, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in rats, using HPLC with electrochemical detection, in 3 brain regions (hippocampus, cerebral cortex and hypothalamus) after acute i.p. treatment with diazepam (4 mg/kg), alprazolam (1.25 mg/kg) or vehicle. In the first experiment, rats received the acute treatment 30 min before they were sacrificed. In the second, the animals were previously habituated to handling (involving the maneuvers of injecting and sacrificing at the guillotine) daily for 15 days, before the acute administration of the drugs. Results of the acute treatment alone showed a significant increase in 5-HT levels in hippocampus and cerebral cortex, and a decrease in hypothalamus, but not differences in 5-HIAA levels, for the diazepam- and alprazolam-treated groups. After handling-habituation, no effect in the monoamine or metabolite levels appeared when the rats were treated with diazepam or alprazolam. The results are discussed in relation to the emotional changes induced by the handling procedure, and for possible connections between the mechanisms of action of handling-habituation and benzodiazepine treatments at CNS level.

Alprazolam↗
PubMed1988

Sodium valproate reduces immobility in the behavioral 'despair' test in rats.

The present study was conducted to investigate whether sodium valproate could affect immobility in the 'behavioral despair' test in rats. Acute (one injection), subacute (three injections) and chronic treatment with sodium valproate reduced the immobility time in this test, whereas a stimulation of motor activity in the open-field test was not observed with the same drug treatments. The anti-immobility activity of valproate was partially counteracted by the administration of bicuculline (2 mg/kg) or picrotoxin (1.4 mg/kg) before the immobility test. The data agree with previous findings from several animal models of depression of an antidepressant-like activity of GABA mimetics or agents which stimulate GABAergic function.

Animals↗