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Biomedical subjects

C M Contreras

Publications and source records attributed to C M Contreras.

At least 37 records · Page 2Linked to original sources

Clomipramine increases firing rate in lateral septal neurons related with hippocampus.

Long-term clomipramine administration (CMI: 2.5 mg/kg IP, 25 days) effects on 274 identified hippocampus-septal neurons was assessed in rats. Stimulation of CA 1/dentate areas produced a biphasic response in 61% of lateral septal neurons. A brief activation was followed by a period of suppression of firing. In CMI-treated rats, the neurons showing this biphasic response increased their firing rate about fourfold, while the suppression of firing shortened around threefold. Other septal neurons (36%), in which only the burst of activation appeared but not suppression of firing, did not change their firing rate even after long-term CMI. In conclusion, CMI produces an increase of firing rate in lateral septal neurons receiving inhibitory hippocampal influence which is likely to be mediated by a disinhibitory process.

Animals↗

A few electroconvulsive shocks produce more reliable effects of firing rate in lateral septal neurons than repetitive treatment in the rat.

Electroconvulsive shock is a common treatment used in depression, especially in cases in which suicide constitutes a risk. The recommendation for its use varies from one place to another, but there is an empirical agreement to avoid daily treatment or several treatments on the same day. The present study explored the actions of electroconvulsive shock in lateral septal firing rate in rats. The first or second once-a-day electroconvulsive shock produced a maximal increase in firing rate; however, effects vanished as treatment was repeated. Three consecutive electroconvulsive shocks on the same day also produced fewer changes in firing rate than once-a-day treatment. These results are likely to be related to clinical recommendations to avoid serial-repetitive treatment, and suggest that some resting time is required in treatment to achieve long-lasting changes in neuronal activity.

Animals↗

Sleep deprivation is a less potent agent than clomipramine in increasing firing rate in lateral septal neurons in the rat.

Acute injection of clomipramine or a 24-hour period of sleep deprivation produces an increased firing rate in lateral septal neurons of the rat. However, it is unknown whether changes in firing rate in lateral septal neurons also appear after repetitive treatments. This study explored and compared the effects of long-term clomipramine with those of sleep deprivation from 1 to 4 days in the firing rate of lateral septal neurons. The firing rate increased after both treatments; however, maximal effects occurred on different days. Clomipramine (1.25 mg/kg, i.p., twice a day) produced a stable, increased firing rate after 20 days of treatment. Twenty-four hours of total sleep deprivation produced changes in firing rate comparable to 10 days of clomipramine treatment. Changes in firing rate did not appear when animals were exposed to 12 h of sleep deprivation alternated with 12 h in housing cages. Therefore, it is concluded that 24 h of total sleep deprivation is a less effective treatment than clomipramine for producing changes in firing rate in lateral septal neurons.

Animals↗

Clomipramine enhances the excitatory actions of dorsal raphe nucleus stimulation in lateral septal neurons in the rat.

Clomipramine is a serotonin reuptake blocker which produces an increased rate of firing in lateral septal neurons of the rat. However, it is unknown whether the response of dorsal raphe nucleus stimulation on the firing rate of the lateral septal neurons is modified by clomipramine treatment. Two programs of stimulation were employed. In the first, iterative stimulation (0.3 Hz, 1 ms, 0.1 mA) produced a complex pattern of response in which activation responses predominated, and clomipramine increased the duration and the firing rate of afterdischarge. In the second program a short train of pulses (300 Hz, 500 ms, 0.1 ms) was applied to the dorsal raphe nucleus. Clomipramine increased both the duration and the frequency of firing with respect to the saline-treated group. The present data show that dorsal raphe nucleus stimulation produces a long-lasting increase in the firing rate of lateral septal neurons which is enhanced by clomipramine. Since clomipramine applied to the septal area produces a decrease in firing, it is concluded that actions taken by clomipramine on raphe nuclei produce a disinhibitory process in the lateral septal neurons.

Animals↗

Clomipramine increases the responsiveness of raphe-cortical neurons in the rat.

The cerebral cortex of the rat possesses 5-HT1A receptor subtype; however, whether the activation of this receptor by dorsal raphe nucleus stimulation produces a similar action on neuronal cortical firing as antidepressants acting on serotonin (5-HT) function is unknown. Single-unit extracellular recordings were obtained from parietal cortex in rats in which dorsal raphe nucleus or cerebellar peduncle was stimulated. Results compared groups long-term treated with clomipramine (1.25 mg/kg i.p., twice a day, during 30 days) or saline (0.15 ml i.p., twice a day, during 30 days). Amplitude of traces, firing rate, and response to treatment with clomipramine proved to be different between cortical neurons responding to dorsal raphe nucleus or cerebellar peduncle stimulation. Clomipramine increased a long-lasting cortical suppression of firing elicited by dorsal raphe nucleus stimulation. Obtained data suggests that the responses of nearby cortical neurons containing different kinds of 5-HT receptors may relate to the involved pathways and that clomipramine seems to act on 5-HT1A receptor subtype.

Afferent Pathways↗

[Anxiety and depression levels in rape offenders].

Whether the active subject of rape possesses a particular personality trait is a much debated matter. It is an accepted fact that a small amount of rapists fall into the sadistic diagnostic category. Other psychopatologic traits likely to identify a rapist are, however, unknown. The present study was carried over at a jail near the city of Xalapa (Veracruz) Mexico. Hamilton, IDARE, and Zung scales, in their modified Spanish version were applied to a sample of imprisoned adult rapists. Compared to their control group (men serving sentences for other felonies), rapists scored higher in anxiety, and depression scales. In the light of these results, it is suggested that some rapists are likely to be anxious-depressive subjects that, after having "acquired" a sociopathic repertoire, offend other people in conditions of indefensiveness, contrary to depressive subjects who aggress themselves.

Adult↗

Chronic clomipramine increases firing rate in lateral septal nuclei of the rat.

A single dosage of several antidepressants produces an increased rate of firing in lateral septal nuclei of the rat. The objective of the present study was to clarify the long-term treatment action of clomipramine on the septal nuclei of the rat. A progressive increase of firing rate appeared after long-term treatment with clomipramine (1.25 mg/kg, IP; twice a day, for 25 days). The most noticeable firing increase occurred in the lateral septal nuclei, which primarily receive serotonergic innervation. Irregular changes occurred in the corpus callosum and cingulum. Finally, in other poorly innervated serotonergic septal regions, the treatment lacked effects. This suggested that the action of clomipramine was primarily due to interaction with the serotonergic system.

Animals↗

Action of antidepressants on the septal nuclei of the rat.

Studies on neuronal firing have shown a decrease in frequency of firing in structures not directly related to emotional processes. However, studies of the hippocampus have shown increases in firing rate. Other limbic structures not yet explored in regard to the action of antidepressants include the septal nuclei. The present work describes a common effect of various therapeutic antidepressant models. Extracellular unit recordings were obtained from the septal nuclei of rats exposed to different acute treatments: clomipramine, isocarboxazid, trazodone, sleep deprivation, and electroshock. Frequencies and firing intervals were analyzed. After treatment, an increase in firing frequency in cells of the dorsolateral septal nucleus was found. This supports the hypothesis that brain structures related to the phenomenon of self-stimulation participate in the mechanism of antidepressant treatments.

Animals↗

Projections of the nucleus accumbens in the cat.

Due to the recent advances in knowledge on the function of the limbic system it would be wise to consider this system as being widely distributed throughout the diencephalic and mesencephalic levels as well as the forebrain. Numerous regions have been discovered that are related to the limbic structures in anatomical and functional respects. According to Koikegami et al. (1967), it would be adequate to divide this system into two main categories--the major limbic rim or the structure proper and the paralimbic structures. The former defined phylogenetically and ontogenetically as those structures around the third ventricle such as: the hippocampus, septum, dentate gyrus, fimbria hippocampi, anterior and posterior cingulate gyri, area paraolfactoria, amygdala and Diagonal Band of Broca. The paralimbic structures may represent those brain regions, which have direct connections or functional correlations with the limbic formation proper. These areas include the posterior orbital gyrus, insula, nucleus accumbens, head of the caudate, nucleus habenula, nucleus interpendencularis, nucleus pulvinaris thalami, intralaminar and anterior thalamic nucleus, preoptic area, hypothalamic nuclei, mammillary body, subthalamus, limbic midbrain area of Nauta, temporal lobe pole, superior temporal gyrus, praecuneus, nucleus dorsalis et profundis tegmenti of Gudden and claustrum. In the present paper we will deal with the projections of the nucleus accumbens. This nucleus was described by Meynert (1872) as the anterior polar region of the caudate nucleus. Kappers describes the nucleus accumbens in 1908 as the nucleus accumbens septi and considers it as a part of the striatum. Later on, the histological studies of Brochaus (1942) relate a part of the nucleus with olfactory functions, and he describes another part, which is very well developed in microsmatic mammals and in anosmic mammals like the dolphin. Szteyn (1960) describes two main areas, the accumbens septi and the accumbens caudate. Nevertheless, the accumbens constitutes a very important region of the paralimbic system and seems to play an important role in some behavioral patterns.

Animals↗

Lateralization of spike and wave complexes produced by hallucinogenic compounds in the cat.

The ability of four hallucinogenic compounds--ketamine, phencyclidine, quipazine, and SKF-10 047--to produce some specific electrical pattern in portions of the limbic system and the hemispheric lateralization of such effects were studied in cats with permanently implanted electrodes. Electronic frequency and area integrators were used to analyze the results, and the percentage change in electrographic alterations was calculated. All compounds studied produced trains of spike and wave complexes in the cingulum, rapid discharges in the amygdala complex, and slow-wave synchronous activity in the septal nucleus. Those changes predominated in the left hemisphere. At small but hallucinatory concentrations of these drugs, the cortical EEG was not affected. Exploratory movements directed toward nonexistent objects, classified as hallucinatory-like behavior, appeared simultaneous with these changes in the EEG recordings. We concluded that there could exist a relationship between the appearance of spike and wave complexes in the limbic system without epileptic signs (twitching or myoclonus) and the presence of hallucinations, and that there is a left side hemispheric lateralization of the electrographic effects, viewing cerebral dominance phenomena as a functional and fluctuating state.

Action Potentials↗

Psychopharmacologic analysis of an alleged oneirogenic plant: Calea zacatechichi.

Calea zacatechichi is a plant used by the Chontal Indians of Mexico to obtain divinatory messages during dreaming. At human doses, organic extracts of the plant produce the EEG and behavioral signs of somnolence and induce light sleep in cats. Large doses elicit salivation, ataxia, retching and occasional vomiting. The effects of the plant upon cingulum discharge frequency were significantly different from hallucinogenic-dissociative drugs (ketamine, quipazine, phencyclidine and SKF-10047). In human healthy volunteers, low doses of the extracts administered in a double-blind design against placebo increased reaction time and time-lapse estimation. A controlled nap sleep study in the same volunteers showed that Calea extracts increased the superficial stages of sleep and the number of spontaneous awakenings. The subjective reports of dreams were significantly higher than both placebo and diazepam, indicating an increase in hypnagogic imagery occurring during superficial sleep stages.

Adult↗

Interhemispheric changes in alpha rhythm related to time perception.

Each cerebral hemisphere processes environmental information in a different but complementary manner. Structures located in the left hemisphere are assumed to participate in symbolic-logic thinking. Time perception may be considered among such thinking processes. The present study evaluates bilateral occipito-central EEG activity in healthy, right-handed subjects which was produced while they performed a visuomotor monitoring task. The task consisted of two stages. The first stage involved the subject's learning a fixed time interval (10 sec) and the measurement of their reaction time. Subjects responded to an isolated light stimulus by pressing a button with the dominant hand. In the second stage, the subjects accuracy in estimating interval-length was evaluated. Two forms of EEG analysis were used, frequency and alpha ratio, each of which was measured both prior to and subsequent to the motor response. A reversal group was used to carry out a complementary test. Subjects responded in the first block of experiments with the non-dominant (left) hand and with the dominant hand in the second. Results showed that left hemisphere activity was continuous during the interval-learning stage and with optimal reaction times and remained continuous when estimation values approximated the real interval. In addition, in optimal reaction time and near to optimal time estimation responses, the left side showed lower frequency and alpha ratio than did the right. Finally a progressive enhancement in both parameters from the right hemisphere was related to deterioration in test performance. Results from the reversal group did not differ from those of the first group. As evaluated by gross measurements of the EEG, a predominant participation of the left hemisphere in time processing is concluded.

Adult↗

Spike and wave complexes produced by four hallucinogenic compounds in the cat.

The ability of four hallucinogenic compounds: ketamine, phencyclidine, quipazine and SKF-10,047 to produce spike and wave activity in the limbic system, was studied in cats with permanently implanted electrodes. Electronic frequency integrators were used to analyze the results and the percent of change in electrographic alterations was calculated. All the compounds studied, produced trains of 6/sec spike and waves complexes in the cingulum, rapid synchronous discharges in the amygdaloid complex, and slow wave synchronous activity and spiking in the septal areas. At low but hallucinatory concentrations of these drugs, the cortical EEG was not affected. Exploratory movements directed toward non-existent objects, classified as hallucinatory-like behavior, appeared simultaneous with these changes in the EEG recordings. It was concluded that there could exist a relationship between the appearance of 6/sec spike and wave complexes in the cingulum and the presence of hallucinations, produced by some synthetic drugs in the cat, this activity could be interpreted as the spreading of altered function of limbic and non-limbic nuclei related with this bundle which explain unspecificity of action.

Animals↗

Petit mal and grand mal seizures produced by toluene or benzene intoxication in the cat.

Motor incoordination, euphoria and hallucinations are symptoms reported for humans voluntarily intoxicated by industrial solvents. An epileptic-like consciousness impairment has also been noted. The present paper describes a technique used for the experimental study of solvent intoxication in which toluene and benzene can be applied directly into the trachea of freely moving cats with chronically implanted electrodes. This technique permits the control of solvent dose and time of exposure. Results showed a 3 Hz spike-wave activity in the gyrus cinguli recording with both toluene or benzene intoxication. Furthermore, benzene inhalation produced generalized tonic-clonic seizures. These effects were dose-related. However, a sensitization period was essential for the development of such alterations, and effects showed a tendency to shortening through chronic exposures. These alterations were correlated with behavioral disturbances such as nodding, twitching and apparent hallucinations. Results are discussed regarding the sensitization period, the optimal peak of effects, and the period of tolerance development relevant to an earlier found amygdalar activation that could be correlated with other methods inducing experimental seizures, such as repetitive stimulation of the brain (kindling).

Amygdala↗

Progesterone reduces immobility in rats forced to swim.

BACKGROUND: Among its behavioral actions, progesterone reduces anxiety in several species including humans; however, any antidepressant-like properties remain to be explored. METHODS: In the present study, Wistar rats received injections (i.p.) of progesterone (0.20-3.0 mg/kg) 24 and 2 h before being submitted to the forced swim, a test in which antidepressants regularly reduce immobility and exert few or no actions on locomotor activity. In order to discard the cumulative effects of progesterone and a possible effect from the repetition of the swimming test, all animals received one of several progesterone doses in a different sequence following a completely randomized experimental intrasubject design. RESULTS: Ovariectomy did not modify immobility in the forced swim test as compared to control tests practiced before surgery. A dose of 0.80 mg/kg strongly reduced the total time of immobility in forced swim test (p < 0.001), but did not modify locomotor activity. In a drug-free control test applied 1 week after the last injection of progesterone, immobility returned to the higher values observed in the control tests. CONCLUSIONS: From these results, it is concluded that progesterone may possess some anti-depressant-like activity.

Animals↗

Septal neurons related with hippocampus increase their firing rate after long-term clomipramine.

In the rat, long-term clomipramine increases the firing rate in lateral septal neurons. Although the hippocampus is the main afference for septal nuclei, it is unknown whether clomipramine increases the firing rate in most of hippocampal-septal neurons. Therefore, the present study explored the actions of long-term clomipramine in lateral septal neurons identified by their relation to the hippocampus. In most recordings, hippocampal stimulation produced a brief excitatory short-latency response, followed by a period of inhibition of firing. These neurons increased their firing rate after clomipramine treatment. Other septal neurons not respondent to hippocampal stimulation did not respond to clomipramine treatment, either. We concluded that only hippocampal-septal neurons are clomipramine responders too, and the drug-induced enhancement of firing rate is likely to be mediated by an interneuron-mediated disinhibition process.

Action Potentials↗