0000000000008869
AUTHOR
Andrés Parra
A common role for psychotropic medications: memory impairment.
Summary The psychopathologic profile of mental disorders is very diverse and psychotropic medications used to treat them differ in their chemical structure. Nevertheless, these drugs share these four characteristics: delayed onset of clinical response, not one of them can be said to cure, there is a high number of non-responders, and the mechanism responsible for their therapeutic action is not known. It is hypothesized that the action of psychotropic medications is memory impairment, understanding memory as the trace left in the nervous system not only by individual experiences but also by genetic and epigenetic phenomena. It is suggested that it would be beneficial to translate some resea…
Are the effects of the antidepressants amitriptyline, maprotiline, and fluoxetine on inhibitory avoidance state-dependent?
Abstract State-dependent learning (SDL) is a phenomenon in which the retrieval of newly acquired information is possible if the subject is in the same physiological state as during the encoding phase. SDL makes it possible to separate the effects of drugs per se on learning from the effects due to changes in drug state during the task. The present work was designed to investigate whether the antidepressants amitriptyline (30 mg/kg), maprotiline (25 mg/kg), and fluoxetine (15 mg/kg) produce SDL of the inhibitory avoidance conditioning in male and female CD1 mice. In three separate experiments, independent groups were used for each pharmacological treatment and for each sex using a 2 × 2 expe…
Changes in brain oxidative metabolism induced by inhibitory avoidance learning and acute administration of amitriptyline
The effects of antidepressant drugs on memory have been somewhat ignored, having been considered a mere side effect of these compounds. However, the memory impairment caused by several antidepressants could be considered to form part of their therapeutic effects. Amitriptyline is currently one of the most prescribed tricyclic antidepressants, and exerts marked anticholinergic and antihistaminergic effects. In this study, we evaluated the effects of inhibitory avoidance (IA) learning and acute administration of amitriptyline on brain oxidative metabolism. Brain oxidative metabolism was measured in several limbic regions using cytochrome oxidase (CO) quantitative histochemistry. Amitriptyline…
Chronic administration of fluoxetine impairs inhibitory avoidance in male but not female mice
The effects of chronic administration of fluoxetine (20 mg/kg/day i.p.) on a one-trial step-through inhibitory avoidance task were investigated in male and female CD1 mice. In Experiment 1, treatment was administered for 21 days before the training session, whereas in Experiment 2, other subjects were subjected to the same treatment starting 24 h after the training session. The comparison of test versus training latencies showed memory deterioration with pre-training administration of fluoxetine (Experiment 1), which affected males but not females. Sex differences in this task were also observed in Experiment 1, with females showing a better performance. Sex differences were evident in cont…
Gender differences in the effects of haloperidol on avoidance conditioning in mice
Abstract Gender differences in the effects of haloperidol (0.07S mg/kg per day for 5 days) on avoidance conditioning were evaluated. We also studied performance of the subjects free of the drug and the acute effects of haloperidol in animals trained without drug 48 h after the last haloperidol administration. Latencies of escape and avoidance responses, number of nonresponses, escapes, avoidances, crossings during the adaptation period, crossings during intertrial intervals, and total crossings per minute were analyzed. This dosage impaired conditioning of the male animals but did not attain the same effects on females. Haloperidol did not deteriorate performance of the task when it had bee…
Piracetam counteracts the effects of amitriptyline on inhibitory avoidance in CD1 mice.
The purpose of the present work was to study the effects of amitriptyline on animal cognition in relation to some characteristics of its therapeutic effects. The modulation of acute and chronic effects of amitriptyline on inhibitory avoidance in male and female mice by piracetam was investigated. In Experiment 1, mice were subjected to the training phase of inhibitory avoidance conditioning 60 min after acute piracetam (100 mg/kg) or physiological saline administration. Immediately after the behavioural task, they received a single injection of the tricyclic antidepressant amitriptyline (30 mg/kg) or physiological saline. Twenty-four hours later, subjects were tested for avoidance. In Exper…
Inhibitory avoidance in CD1 mice: sex matters, as does the supplier.
The purpose of the present work was to study possible differences in the learning of inhibitory avoidance (also called passive avoidance) in male and female CD1 mice acquired from three different suppliers, for which a one-trial step-through version of the paradigm was employed. Ninety-six mice from Charles River (France), Janvier (France) and Harlan (The Netherlands) laboratories were divided by sex and assigned to group C, J or H, respectively (n=16). The animals were tested in the training phase (foot-shock: 0.3mA, 5s) and again for avoidance (no foot-shock delivered) one week later. Inhibitory avoidance learning (test latencies significantly higher than training latencies) was observed …
Sex differences in the effects of neuroleptics on escape-avoidance behavior in mice: a review.
Abstract The literature of the effects of dopamine antagonists on escape-avoidance, focusing on data obtained in our laboratory with male and female mice, is reviewed. The acute administration of haloperidol, raclopride, clozapine, and SCH 23390 impaired escape-avoidance behavior more in males than in females, and the subchronic administration of haloperidol had a similar effect. This appeared to be a reliable phenomenon, because it was observed in both kinds of administration, in two mouse strains, and with several drugs and doses. The observed results were dose dependent, although the dose–effect relationship was not the same in all drugs. The sex differences in escape avoidance did not s…
Coffee increases state anxiety in males but not in females.
Coffee, reproducing the conditions under which caffeine is normally ingested, containing 3, 75, 150 or 300 mg of caffeine was given to healthy male and female volunteers. 25-30 min after drinking the beverage, they completed the Spanish version of the state-trait anxiety inventory (STAI). The beverage increased state anxiety, in a dose-dependent manner, in males but not in females. This could be due to a lesser sensitivity of females to coffee.
Sex differences in estimation of time intervals and in reaction time are removed by moderate but not high doses of caffeine in coffee
Estimation of the passage of time in the seconds-to-minutes range and reaction time are strongly dependent on a hypothetical internal clock. Dopamine is the neurotransmitter most closely related to the rate of this clock. Caffeine, probably the most consumed drug in the world, leads to an augmentation of dopamine neurotransmission. In this study coffee, which reproduces the conditions under which caffeine is normally ingested, containing 3, 75, 150 or 300 mg of caffeine, was given to healthy male and female volunteers. A computerized time estimation and reaction time test was carried out 50 min after ingestion. Sex differences in placebo control subjects (who took decaffeinated coffee with …
Effects of acute amitriptyline administration on memory, anxiety and activity in male and female mice
The effects of acute administration of amitriptyline on memory consolidation in male and female CD1 mice were investigated. Three doses of this tricyclic antidepressant (7.5, 15 and 30 mg/kg) were administered immediately after inhibitory avoidance training. Forty-five minutes after injection, subjects explored the elevated plus-maze for five minutes. Subjects were tested for avoidance twenty-four hours later. Amitriptyline impaired inhibitory avoidance consolidation at doses 7.5, 15 and 30 mg/kg in males, and at doses 7.5 and 30 mg/kg in females. In the elevated plus-maze, amitriptyline had no effect on anxiety (percentage of open arm entries) and induced a dose-dependent impairment of act…
Predicting how equipotent doses of chlorpromazine, haloperidol, sulpiride, raclopride and clozapine reduce locomotor activity in mice
Distinguishing the specific effects of neuroleptics on one particular behaviour from its non-specific effects on motility is not easy. In this study, the effects of five neuroleptics on spontaneous motor activity were compared and the ED(50) values of these drugs to impair activity were calculated. Male and female mice were evaluated in an actimeter or in a shuttle-box used as an open field after the administration of chlorpromazine (0.4, 1.2, 3.6 mg/kg), haloperidol (0.1, 0.3, 0.9 mg/kg), raclopride (0.1, 0.3, 0.9 mg/kg), sulpiride (10, 30, 90 mg/kg) and clozapine (0.4, 1.2, 3.6 mg/kg), and two automatic and two observational activity measures were obtained. A very high correlation between…
Antidepressant drugs and memory: Insights from animal studies
This is a selective review of the literature concerning the effects of antidepressant drugs on animal memory, which was performed with the aid of the PubMed database. Monoamine oxidase inhibitors tend to either have no effect on memory or result in its improvement. Studies with cyclic antidepressants have reported no effect or, more often, memory impairments. Pre-training administration of selective serotonin reuptake inhibitors (SSRIs) has been shown to have either no effect on memory or undermine it (with some isolated exceptions, in which improvements have been recorded), while post-training administration of SSRIs has been demonstrated to improve memory or have no effect. A small group …
Effects of co-administration of amitriptyline and fluoxetine on inhibitory avoidance in mice
We have previously observed that, while the impairing effects of amitriptyline on inhibitory avoidance in mice are consistently observed, those of acute fluoxetine are negligible. Two experiments were designed to investigate whether a regular dose of fluoxetine potentiates the effect of a low dose of amitriptyline that is ineffective when administered alone. Male and female CD1 mice were administered i.p. 30 min before training, as follows. In the first experiment, they were injected with saline, one of three doses of amitriptyline (2.5, 5, 10 mg/kg), one dose of fluoxetine (15 mg/kg), or a combination of amitriptyline (2.5 mg/kg) and fluoxetine (15 mg/kg). In the second experiment, the mic…
Effects of Antidepressants on Inhibitory Avoidance in Mice: A Review
Neither the biological basis of depression (Nemeroff & Vale, 2005; Kasper & McEwen, 2008) nor the precise mechanism of antidepressant efficacy are completely understood (Dudra-Jastrzebska et al., 2007). Indeed, antidepressants are widely prescribed for anxiety and disorders other than depression. For example, they are the drug therapy of choice for severe anxiety disorders such as agoraphobia, generalized anxiety disorder, social phobia, obsessive-compulsive disorder and post-traumatic stress disorder (Baldessarini, 2001). Antidepressants are also employed as a therapeutic tool in disorders such as drug addition (e.g. Schatzberg, 2000), enuresis (e.g. Humphreys & Reinberg, 2005) and chronic…
Dose Dependency of Sex Differences in the Effects of Repeated Haloperidol Administration in Avoidance Conditioning in Mice
Sex differences in the effects of haloperidol in active avoidance conditioning in mice have previously been found in various studies carried out in our laboratory. Males were more affected than females by the disruptive effects of this neuroleptic. The work described here broadens the study of these sex differences to higher doses of haloperidol (0.1 and 0.2 mg/kg) using a repeated administration schedule (5 days). The results did not show sex differences in the deteriorating effects of this dopamine antagonist in the escape-avoidance response, but a tendency in the number of nonresponses was observed in the same direction as former results: male animals were more sensitive than females to …
Sex differences in escape-avoidance response in mice after acute administration of raclopride, clozapine, and SCH 23390.
Sex differences in the effects of haloperidol in the escape-avoidance response in mice have previously been found in various studies carried out in our laboratory. Males were more affected than females by the disruptive effects of this neuroleptic. The work described herein extended the study of these sex differences to raclopride, clozapine, and SCH 23390, using several doses of each drug in acute administration. The results showed dose-dependent sex differences in the deteriorating effects of these dopamine antagonists in the escape-avoidance response. Male mice were more affected by the inhibitory effects of these drugs, showing fewer escape responses and more nonresponses than females. …
An ethological analysis of the effects of diazepam and nitrazepam on the responses of female mice to anosmic males encountered in a novel arena
The effects of acutely administered benzodiazepines have largely been validated in male animals, in spite of the fact that the majority of anti-anxiety drugs are prescribed for female patients. A study was carried out assessing the potential of female mice in the testing of the anxiolytic properties of drugs. Three doses (0.5, 1.0 and 2.0mg/kg) of the benzodiazepines diazepam and nitrazepam were given to individually-housed female Swiss mice before dyadic encounters with anosmic, group-housed males. Videotape analysis of the encounters, using an ethopharmacological technique, revealed suppressive effects of diazepam (1.0 and 2.0mg/kg) and nitrazepam (all doses) on avoidance/flee, confirming…
Coffee and Anxiety
Abstract This chapter discusses the effects of coffee consumption on anxiety response, taking into account vulnerability factors such as sex and genetics. In light of research concerning the effects of coffee on normal anxiety, and particularly research carried out in our laboratory, current knowledge can be summarized as follows: (1) men appear to be more sensitive to the effects of coffee than women; and (2) coffee can increase alertness in habitual consumers after acute deprivation, but not above the level of that observed in nonconsumers. In addition, we discuss clinical evidence of the varying sensitivity of anxiety disorder patients to the effects of coffee. The caffeine challenge tes…
Effects of oxotremorine and physostigmine on the inhibitory avoidance impairment produced by amitriptyline in male and female mice.
We have previously observed that amitriptyline and other antidepressants produce impairing effects on inhibitory avoidance (also called passive avoidance) in mice of both sexes. In the present study we investigated the involvement of the cholinergic system in the inhibitory avoidance impairment produced by acute amitriptyline in male and female CD1 mice. For this purpose, the effects on said task of acute i.p. administration of several doses of amitriptyline, either alone or in combination with the cholinergic agonists oxotremorine and physostigmine, were evaluated. Pre-training administration of 5, 7.5, 10 or 15 mg/kg of amitriptyline produced a significant impairment of inhibitory avoidan…
Attenuation of sucrose consumption in mice by chronic mild stress and its restoration by imipramine
Chronic exposure to mild unpredictable stressors (CMS) has previously been found to reduce the consumption of palatable, sweet solutions in rats. In the present study, the utility of this procedure was assessed in mice. Male AP mice subjected to CMS showed reduced consumption of a 2% or 4% sucrose solution. This effect was reversed by chronic (3 weeks) treatment with the tricyclic antidepressant imipramine (20 mg/kg per day). These results extend previous reports of a generalized decrease in sensitivity to reward (anhedonia) in rats caused by CMS and the efficacy of antidepressant treatment in this paradigm. Chronic unpredictable mild stress in mice appears to provide a realistic animal mod…
Apparent vs real effects of scopolamine on the learning of an active avoidance task.
The effects of scopolamine hydrobromide (0.5 and 2 mg/ kg) administered intraperitoneally to Balb/c male mice before or after training in active avoidance were explored in four training sessions and in a subsequent test session, free of drug. Animals given scopolamine prior to training performed better than controls, an effect that was reversed in the session free of drug. However, a deeper analysis of the data permits us to interpret this increment in the number of avoidance responses as a consequence of the increase in activity produced by the drug and not as learning. In the animals injected with scopolamine after sessions no effects were observed. In conclusion, the results of the prese…
Effects of Alcohol, Coffee, and Tobacco, Alone or in Combination, on Physiological Parameters and Anxiety in a Young Population
The objective was to evaluate the effects of a single dose of alcohol, caffeine, and nicotine, alone or in combination, on physiological parameters (systolic and diastolic blood pressure [SBP and DBP] and heart rate [HR]) and state-trait anxiety in healthy young volunteers.The procedure reproduces the conditions under which the subjects (Intake of alcohol or alcohol-nicotine reduced DBP. Comparisons between control and combined treatment (coffee-alcohol-nicotine) groups revealed a decrease in HR in the former group but not in the latter. The coffee consumers alone exhibited a tendency toward an increase in SA, while the control group showed a tendency toward a decrease in this measure. When…
Gender differences in escape-avoidance behavior of mice after haloperidol administration.
Gender differences in the disruptive effects of haloperidol on some reinforced behaviors have been observed in different species. However, the inhibitory action of haloperidol on the acquisition and performance of escape-avoidance behavior has only been investigated in male subjects. The present experiment was designed to investigate possible gender differences in the effects of haloperidol on the initial phase of an escape-avoidance learning task. Male and female mice of the OF1 strain were given a single training session in a shuttle-box. Thirty minutes prior to the behavioral test, mice were injected IP with haloperidol (0.25 mg/kg) or physiological saline (10 ml/kg). Latencies of escape…
The Higher the Dose, the Greater the Sex Differences in Escape–Avoidance Response in Mice After Acute Administration of Haloperidol
Abstract MONLEON, S. AND A. PARRA. The higher the dose, the greater the sex differences in escape–avoidance response in mice after acute administration of haloperidol . PHARMACOL BIOCHEM BEHAV 60 (1) 279–284, 1998.—Sex differences in the effects of haloperidol in the escape–avoidance response have previously been found in various studies carried out in our laboratory in which mice were used as experimental subjects. Males were more affected than females by the disruptive effects of this neuroleptic of frequent clinical use. In the present work these sex differences were evaluated in a unique training session using several doses of the drug (0.075, 0.25, and 0.75 mg/kg IP). The number of avo…
Efectos fisiológicos y psicológicos de una alta dosis de alcohol en hombres y mujeres jóvenes
El objetivo de este estudio fue evaluar los efectos de una dosis alta de alcohol sobre parametros fisiologicos y psicologicos en hombres y mujeres jovenes con historia previa de consumo de alcohol. La presion sanguinea sistolica y diastolica, la frecuencia cardiaca, la ansiedad estado, el procesamiento atencional, la estimacion temporal y la destreza manual fueron registradas antes (fase 1) y despues (fase 2) de la ingesta de alcohol (38,4 g) o de una bebida no alcoholica. La ansiedad rasgo fue registrada solamente en la fase 2. Los resultados mostraron que el consumo agudo de una dosis alta de alcohol: i) en hombres, mejora el procesamiento atencional (aunque la ejecucion de los consumidor…
Effects of acute and chronic maprotiline administration on inhibitory avoidance in male mice
The effects of acute and chronic administration of maprotiline (5, 10 or 20 mg/kg, intraperitoneally) were assessed on inhibitory avoidance in male mice. Acute administration of maprotiline before training did not effect training phase latencies, but impaired performance (i.e. produced shorter latencies) in the test at doses of 5 and 20 mg/kg. When given after training, the drug did not modify test latencies at any of the doses used. Chronic administration for 21 days (interrupted 24 h before training) also shortened latencies in the test but not in training. An experiment on the acute effects of maprotiline on analgesia (determination of flinch and jump thresholds for increasing electric f…