Fear induced by the blockade of GABAA-ergic transmission in the hypothalamus of the cat: behavioral and neurochemical study.

Intrahypothalamic injections of d-Tubocurarine (DT) and bicuculline (BM) in the cat produced a fear reaction characterized by terrific mewing, increased locomotor activity, jumps and attempt to escape from the chamber, pupillary dilatation, increased respiratory rate, and sometimes urination and defecation. HPLC analysis showed a significant increase in the noradrenergic system activity in the emotional brain areas (hypothalamus, midbrain, amygdala) and frontal cortex at the time of the fear drive. No changes in the cat's behavior and in the monoaminergic systems activity occurred after muscimol+d-Tubocurarine injections into the hypothalamus. Similar behavioral and neurochemical effects evoked by DT and BM suggest that the fear response evoked by DT does not result from the blockade of N-cholinergic transmission but rather from their action on GABAA receptor complex. The results obtained indicate that the central triggering mechanism for fear drive depends on the blockade of GABAA-ergic transmission.

[Osteogenesis during the correction of burns with alpha-tocopherol]. / Osteogenez pri korrektsii ozhogovoi bolezni al'fa-tokoferolom.

Macro- and microscopic transformations were studied in burned animals skeleton after treatment with alpha-tocopherolum. The antioxidant was found to optimize osteogenesis, disturbed in burn lesion.

The effects of dorsal and ventral noradrenergic system lesions with DSP-4 on emotional-defensive behavior and regional brain monoamines content in the cat.

As a result of selective lesions of dorsal (DB) and ventral (VB) noradrenergic system (DSP-4 i.c.) it was observed that these two systems are functionally differentiated and only DB participates in the regulation of post-carbachol emotional-defensive behavior in the cat. Following DB lesion an increase in emotional-defensive excitation occurred and HPLC analysis showed a significant reduction of NA concentration in the posterior hypothalamus, midbrain central gray matter and frontal cortex and decreased turnover of 5-HT in all "emotional brain areas" (hypothalamus, midbrain, amygdala, hippocampus) and frontal cortex. Following VB lesion there were no significant changes of post-carbachol defensive behavior and HPLC analysis showed a significant reduction of NA in the anterior and posterior hypothalamus, midbrain central gray matter and amygdala and an increased turnover of 5-HT in the posterior hypothalamus and midbrain central gray matter. The results obtained can be interpreted in relation to functional interactions between the NA and 5-HT systems.

The participation of serotoninergic system in the regulation of emotional-defensive behavior evoked by intrahypothalamic carbachol injections in the cat.

The influence of bilateral injections of serotonin (5-HT) and methysergide (MET) to antero-medial hypothalamus (HA) on carbachol-induced emotional-defensive behavior was investigated. Earlier (15 min) stimulation of 5-HT receptors in HA region by 5-HT injections evoked a decrease in the level of vocal response (number and time of growling), while previous blocking of these receptors by means of MET brought about a considerable increase of vocalization level evoked by carbachol (Cch) injections (10 pg) to the same loci of HA. Intrahypothalamic injections of 5-HT alone or MET did not evoke any observable changes in the animals behavior. The alterations of the level of Cch-induced vocal response 3 to 35 days after chemical damage of 5-HT neurons in HA or in the middle forebrain bundle (MFB) in posterolateral hypothalamus caused by 5,7-dihydroxytryptamine were examined. Local neurotoxin injections both to MFB and to HA evoked a long lasting increase in the level of Cch-induced vocalization, which began on the 5th-7th day after lesioning and lasted till the completion of the experiment (35 days). Results data indicate that the 5-HT system exerts an inhibiting influence on the emotional-defensive behavior induced by the cholinergic system.

The effects of external stimuli on the emotional-aversive response evoked by intrahypothalamic carbachol injections.

The aim of this investigation was to examine the effects of threatening (the sight and barking of the dog) or "Neutral" (flash and tone) stimuli on the emotional-aversive response evoked by direct intracerebral application of carbachol in cats. Unilateral microinjections of carbachol in 10 microgram doses and 2 mu1 volume into anterior hypothalamic/preoptic area caused a full-blown emotional response with marked vocalization. All stimuli which might be threatening for cats caused a significant increase of vocalization. "Neutral" stimuli of comparable intensity were without effect. To investigate the effects of stimulation intensity two clocks: low and loud (difference of 27 dB), were used. The loud click significantly increased vocalization level while the low click of the same intensity as a dog's barking had no significant influence on the carbachol-induced response. Cholinergic stimulation of the anterior hypothalamic/preoptic area seems to be specifically responsible for the obtained change of perception towards increased sensitivity to any potentially threatening alteration of the environment.

Adrenergic modulation of the hypothalamic cholinergic mechanism in the control of emotional-defensive behavior in the cat.

Effects of drugs influencing the activity of the hypothalamic noradrenergic system on the carbachol-induced emotional-defensive response were investigated. Intrahypothalamic injections of noradrenalin, amphetamine and reserpine did not produce any changes in cats' behavior. Injections of carbachol into the same hypothalamic loci, following the injections of noradrenalin, amphetamine or reserpine evoked all the characteristic symptoms of emotional-defensive behavior. However, a strong decrease in the number of growls and the duration of growling was observed when reserpine injections preceded the injections of carbachol into the same hypothalamic areas. Adrenergic alpha and beta agonists (methoxamine and isoprenaline) as well as antagonists (phentolamine and oxprenolol) when injected alone had no influence on the cats' behavior. Their effect on vocal responses evoked by subsequent injections of carbachol was not statistically significant. Results show that emotional-defensive behavior cannot be triggered by an activation of the hypothalamic noradrenergic system. However, emotional defensive behavior induced by cholinergic stimulation of the hypothalamus may be modified by changes in the activity of the hypothalamic noradrenergic system.

Midbrain interaction with the hypothalamus in expression of aggressive behavior in cats.

The effects of injections of M- and N-cholinergic blocking agents into the antero-medial hypothalamus (HM) and the midbrain central gray (GC) on the aggressive behavior of cats, evoked by microinjections of carbachol into those areas, were investigated in chronic experiments. The influence of pharmacological suppression of the M-cholinergic system in HM on the carbachol-induced aggression response from GC and vice versa was also studied. In the experiments a quantitative method was applied for measuring the specific vocalization - growling, which is a characteristic of aggressive behavior. In the HM and GC areas of the cat the N- and the M-cholinergic systems participated in the control of aggressive behavior, but the M-component dominated in the process. The suppression of M-cholinergic system in GC prevented the appearance of aggressive behavior evoked by injections of carbachol into HM, and the M-cholinergic blockade in HM reduced (by 90 percent) the aggression response evoked by the injections of carbachol into GC. It is concluded that a concurrent action of the hypothalamic and the midbrain cholinergic systems is necessary for the appearance of a fully expressed aggressive behavior. The hypothalamus and the midbrain are probably links of the same functional circuit, and that the control of aggressive behavior is based on a circulatory action between these structures.

Comparison of defensive behavior evoked by chemical and electrical stimulation of the hypothalamus in cats.

Comparison of defensive behavior evoked by chemical anf electrical stimulation of the hypothalamus in cats. Acta Physiol. Pol. 1975, 26 (1) 23--31. An injection of 5 mug of carbachol, as well as electrostimulation of the same hypothalamic area evoked in cats the same type of defensive behavior -- rage reaction. Experiments with carbachol injection and electrostimulation after blockade of the hypothalamic muscarinic receptors (10 mug of atropine) indicate that rage reaction is evoked in a different way by the two methods. Controversial data regarding localization of the hypothalamic "centres" responsible for particular type of defensive reactions are discussed.

Neurochemical bases of defensive behavior in animals.

This paper presents a literature review and the author's own investigations devoted to identifying the morphological organization of different subcortical structures and neurochemical processes involved in the (regulation of defensive behavior. The effects of intrahypothalamic injections of two cholinomimetic substances, carbachol and d-tubocurarine, on rage and fear reactions were explored. Also the investigations were carried out with intrahypothalamic injections of anticholinergic substances, atropine and betamon or hexamethonium, which block selectively muscarinic and nicotinic receptors. The results indicate that carbachol injected into the hypothalamus after blocking the muscarinic receptors with atropine fails to elicit any defensive response; whereas carbachol injection administrated after nicotinic receptors had been blocked by betamon or hexamethonium induces full aggressive behavior. This indicated that carbachol acts, on the hypothalamic level, through the muscarinic receptors. The mechanism of d-tubocurarine action seems to be more complex because this compound induces fear response after either the muscarinic or the nicotinic receptors have been blocked. A possible mechanism based on chemically differentiated neuronal circuits at the hypothalamic level for two different defensive drives, fear and rage, is presented.