L. Valzelli

Studies on behavioral and biochemical changes in rats after lesion of midbrain raphé

Abstract Lesions of the midbrain raphe in rats produced a marked decrease of 5-HT and 5-HIAA levels in the forebrain. An increase of spontaneous motor activity and an onset of signs of abnormal behaviour were observed. A good correlation has been found between the intensity of behavioural excitation and the decrease of 5-HT and 5-HIAA in the forebrain. Bioelectrical investigations of frontal cortical activity showed a persistent arousal in EEG pattern.

Reduced effect of morphine in midbrain raphe lesioned rats

Abstract The reaction of painful stimulation was studied in rats by means of three different techniques. Lesions of the midbrain raphe in rats, which reduced the levels of brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) decreased the analgesic activity of morphine. In some tests, an increase in sensitivity to painful stimulation was noted in lesioned animals. The results obtained support the view that a decrease of brain 5-HT concentration antagonizes morphine analgesia. The possible role of the other brain monoamines in the analgesic activity of morphine is also discussed.

The effects of selective lesioning of brain serotonin or catecholamine containing neurones on the anorectic activity of fenfluramine and amphetamine

Abstract The effects of fenfluramine and amphetamine on food intake were studied in midbrain raphe-lesioned or in 6-hydroxydopamine-treated rats. Lesion of the midbrain raphe, which lowers forebrain serotonin, antagonized the anorectic effect of fenfluramine but did not modify the action of amphetamine. An intraventricular injection of 6-hydroxydopamine, which produced a marked decrease of brain noradrenaline and dopamine, did not affect the actions of either amphetamine or fenfluramine. A possible role of brain serotonin and catecholamines on anorexia induced by amphetamine and fenfluramine is discussed.

Electrical stimulation of midbrain raphe: Biochemical, behavioral and bioelectrical effects

Abstract Electrical stimulation of MR in rats induces a marked increase of 5HIAA and a decrease of 5HT in the forebrain. At the same time the onset of electroencephalographic pattern of sleep and behavioral signs of calmness were observed. The most intense biochemical effects were obtained with 10 c/sec stimulation whereas 2 c/sec stimulation produced the clearest behavioral depression. 5HT Midbrain raphe 5HIAA Electroencephalographic changes Behavior Sleep pattern Electrical stimulation

Anxiolytic activity on locus coeruleus-mediated suppression of muricidal aggression☆

The evidence suggests that stimulation of brain noradrenergic neurons plays an inhibitory role in rat mouse-killing (muricidal) aggression. Anxiolytic benzodiazepines inhibit locus coeruleus activity and previous data showed that chlordiazepoxide was capable of antagonizing the locus coeruleus-mediated suppression of muricidal aggression. The present experiments showed that this effect is common to new anxiolytic triazolobenzodiazepines and to other non-benzodiazepine derivatives with anxiolytic activity. In this framework, 10 mg/kg of buspirone, of 1-pyrimidine-piperazine and of MJ-13805 proved to be as active as 2.5 mg/kg of alprazolam and as 5 mg/kg of chlordiazepoxide in inhibiting the locus coeruleus-mediated suppression of muricidal aggression.

Activity of desipramine, fluoxetine and nomifensine on spontaneous and P-CPA-induced muricidal aggression

Antidepressant drugs reportedly counteract mouse-killing activity by rats. There is evidence that antidepressant derivatives exert their anti-muricidal activity through both noradrenergic and serotonergic neurons. The experiments were performed in two types of muricidal aggression with three antidepressants characterized by different neurochemical activity. No major differences in the antimuricidal efficacy of the drug-employed were found, even though spontaneous muricidal animals resulted on the whole less sensitive to antidepressants than p-CPA-induced muricidal rats. In these last animals nomifensine proved to be more potent than desipramine and fluoxetine.

Is the isolated animal a possible model for phobia and anxiety

Abstract 1. 1. Isolated animals develop a complex symptopathology which can be characterized both behaviorally and neurochemically. 2. 2. The main behavioral features include: compulsive aggression, impairment of learning, exploration and sexual behavior, while the main neurochemical features include a decrease of brain tryptophan content and of brain serotonin turnover and an increased brain dopamine turnover. 3. 3. Isolated aggressive mice are differently sensitive than grouped animals and respond differently to several psychotropic drugs, tricyclic antidepressants, betablockers and benzodiazepines. 4. 4. The results obtained will be discussed in the frame of the possibility of utilizing these animals models to study drugs active on anxiety and phobia.

Norepinephrine-mediated suppression of apomorphine-induced aggression and locomotor activity in the rat amygdala

The effect of injections of norepinephrine (NE)-depleting toxin DSP-4 into the central amygdala (AMY) on apomorphine-induced fighting (AIF) was studied. In addition, the influence of such treatment on related parameters such as spontaneous activity, pain sensitivity and changes in locomotion after (+)3-PPP or apomorphine (1 mg/kg SC each) were verified. Finally, injections of NE or phenylephrine into the AMY five min before AIF were performed. DSP-4 induced marked (-71%) and selective fall in NE within the AMY accompanied by significant increase in aggressive response to 5 mg/kg of apomorphine. DSP-4-treated animals were less active in the open field and more sensitive to pain in a hot plate test. They were also more responsive to locomotor-augmenting action of apomorphine. Significant suppression of AIF was seen after injections of NE and phenylephrine into the AMY. The results suggest that NE input to the AMY plays an inhibitory role in dopamine-related locomotion and aggressivity. Moreover, amygdalar NE appears to be involved in general activity and pain perception modulation.

Effect of 6-OHDA injected into the locus coeruleus on apomorphine-induced aggression

Bilateral microinjections of 6-hydroxydopamine (6-OHDA) into the nuclei loci coerulei (LC) of male Wistar rats resulted in significant depletion of mesencephalic and striatal norepinephrine, accompanied by a small reduction in dopamine content only in the striatum. Apomorphine (2.5 mg/kg IP) induced marked aggression consisting of prolonged posturing, vocalization and attacks only in 6-OHDA lesioned animals. Biochemical analysis revealed that 6-OHDA antagonized the ability of apomorphine to raise the serotonin concentration in the striatum. It is concluded that the LC neurons play an inhibitory role in apomorphine-induced aggressiveness and the involvement of serotonergic neurons is suggested.

Effect of stimulation of midbrain raphe on serotonin (5-HT) level and turnover in different areas of rat brain.

Abstract Stimulation of the nucleus medianus of the midbrain raphe in rats caused an increase of 5-HT turnover in the forebrain without changes in the 5-HT turnover of the posterior part of the brain and of the spinal cord.