Enkephalinergic mechanisms in midbrain (dPAG) in modulation of hypothalamically-induced predatory attack behaviour.

Present study was carried out in nine cats which did not attack the rats spontaneously. Predatory attack on an anaesthetized rat was elicited by electrical stimulation of lateral hypothalamus at a mean current strength of 690 microA. The attack was accompanied by minimal affective display and culminated in neck biting. Microinjections of delta-alanine methionine enkephaline (DAME) in 250 ng dose in dorsal periaqueductal gray completely suppressed the predatory attack. There was a significant increase in the threshold current strength for affective display components while the somatic components were completely inhibited even when the current strength was increased to 1000 microA. Microinjections of naloxone, an opioid antagonist in 1 microgram dose reversed the DAME blocking effect and the thresholds returned to control levels within 10 min of microinjections. Microinjections of naloxone alone in similar dose facilitated the response as indicated by a decrease in threshold current strengths for both affective display and somatomotor components. Control injections of saline in similar volumes (0.5 microliter) failed to produce any change. These findings indicate that hypothalamically induced predatory attack is inhibited by enkephalinergic mechanisms operating at the dPAG level in the midbrain.

Role of midbrain ventro-lateral tegmental area (VTA) enkephalinergic mechanisms in the facilitation of hypothalamically-induced predatory attack behaviour.

Bipolar concentric electrodes were implanted in five cats in extreme lateral regions of hypothalamus. These sites were electrically stimulated using biphasic square wave pulses at a current strength ranging from 300-800 microA to evoke predatory attack on an anaesthetized but live rat. At lower current strength (300 microA) only alertness with pupillary dilatation was produced. Gradual increase in the current strength led to the recruitment of somatic and affective components and a predatory attack was exhibited at a mean current strength of 700 microA. A scoring system allowed the construction of stimulus response curves, which remained fairly constant when repeated over a period of 3-4 weeks. Bilateral microinjections of delta-alanine methoinine enkephaline (DAME) (500 ng in 0.5 microliter saline) in ventrolateral tegmental area (VTA) elevated the mean threshold current strength for affective components while somatomotor components were totally inhibited. The blocking effect of DAME persisted for 1 hour. Microinjections of naloxone (1 microgram) in similar volumes facilitated the response as indicated by a reduction in threshold current strength for somatomotor and affective components. Microinjections of naloxone (1 microgram) in similar volumes facilitated the response as indicated by a reduction in threshold current strength for somatomotor and affective components. Microinjections of naloxone (1 microgram) also reversed the blocking effect of DAME and the thresholds returned to the control level within 10 min while microinjection of normal saline as control had no effect. The excitatory effects of naloxone and inhibitory effects of DAME were statistically significant at P < 0.01 and P < 0.05 respectively with Wilcoxon's signed rank test. The present study indicates that enkephalinergic as well as opioidergic mechanisms operating at the midbrain (VTA) level are involved in the inhibition of predatory attack as elicited from lateral hypothalamus.

Role of midbrain ventro-lateral tegmental area (VTA) adrenergic mechanisms in facilitation of hypothalamically-induced predatory attack behaviour.

Bipolar concentric electrodes were implanted in extreme lateral regions of hypothalamus having coordinates (A12.5 mm, L 3.5-3.7 mm, V 3.0-3.7 mm). These sites were electrically stimulated using biphasic square wave pulses (1 ms, 60 Hz) at a current strength ranging from 300-800 microA to evoke predatory attack on an anaesthetized rat. At lower current strengths of 300 microA only altertness with pupillary dilatation was produced. Gradual increase in the current strength led to recruitment of somatic and affective components and a full blown predatory attack on a rat was produced at a mean current strength of 700 microA. A scoring system allowed the construction of stimulus response curve, which remained fairly constant when repeated over a period of 3-4 weeks. In ventrolateral tegmental area (VTA), bilateral microinjections of norepinephrine (NE 10 micrograms in 0.5 microliter saline, pH 7.4) lowered the mean threshold current strength to 100 microA while predatory attack was produced at 500 microA. Clonidine (5 micrograms in 0.5 microliter propylene glycol, pH 7.4) an alpha-2 agonist similarly lowered the mean threshold to 100 microA and predatory attack threshold to 400 microA. The effects of clonidine appeared within 20 min of microinjection and persisted up to 6 hr. Yohimbine, an alpha-2 antagonist (4 micrograms in 0.5 microliter propylene glycol. pH 7.4) when microinjected into the same locus (VTA), completely blocked predatory attack behaviour for 3 days, the peak period of the blocking effects were between 3-8 hr, after microinjection. Isoproterenol (beta agonist), propranolol (beta blocker), prazosin (alpha-1 antagonist) and phenoxybenzamine (alpha antagonist) failed to produce any effect. Normal saline and propylene glycol in similar volumes served as controls. The excitatory effects of NE and clonidine and inhibitory effects of Yohimbine were significant at P < 0.01 and P < 0.05 respectively with Wilcoxon's signed rank test. The present study indicates the involvement of alpha-2 adrenoceptive mechanisms operating at the midbrain (VTA) level in the elicitation of predatory attack from lateral hypothalamus.

Vasopressor responses in autosomal dominant cerebellar ataxia.

Thirteen patients with autosomal dominant cerebellar ataxia were investigated for autonomic functions using standard tests. Patients showed no significant reduction in parasympathetic responses as measured by heart rate response to slow breathing and Valsalva manoeuvre. Measurement of blood pressure response to isometric exercise, cold exposure and 70 degrees head-up tilt showed a significant decrease in sympathetic pressor response.

Electrical and chemical stimulation of the same hypothalamic loci in relation to agressive behaviour in cats: a comparison study.

Chemitrodes which permit electrical and chemical stimulation of the same hypothalamic loci were implanted in anterior hypothalamic and preoptic regions. These sites were stimulated electrically using biphasic square wave pulse (1 ms, 60 Hz) at a current strength ranging from 150-800 microA to evoke an aggressive response. At lower current strength of 150-200 micro A, defence response, a sort of non-specific response can be elicited from these regions. Increasing the current strength to 400 microA led to the recruitment of affective and somatic components and changed the response pattern either to affective attack or flight. The loci producing affective attack response were localized more laterally and ventrally while the loci producing flight response were located in the dorsomedial regions of the hypothalamus. In this response the animal made a goal-directed attempt to escape through an escape route. Increasing the current strength to 500 microA in the dorsomedial regions changed the flight response to violent flight, which involved vigorous running with unsheathed claws and attacking objects if obstructed. Similar increase in current strength at loci producing affective attack only led to a decrease in the latency of response and made the attack more vigorous. Microinfusion of carbachol in graded doses of 2-15 microgram at all these loci produced a profound affective display. At lower doses of 2 and 5 microgram, only some components of affective display like alertness, pupillary dilation and ear flatness were exhibited. Increasing the dose to 10 micrograms and 15 micrograms led to the recruitment of other affective components like piloerection, salivation, hissing and baring of teeth. Microinfusion of carbachol at all loci producing affective attack on electrical stimulation produced a prononced affective display while microinfusion of carbachol at loci producing flight response led to the development of defence posture. At six loci a typical flight response was obtained while violent flight was never exhibited at any of these sites. Microinfusion of atropine (10 microgram in 1.0 microliter saline) at these loci completely blocked the carbachol induced response. Both somatomotor and affective components were completely inhibited. However, the responses obtained on electrical stimulation were not totally blocked following atropine infusion and some of the somatomotor and affective components could be elicited with higher current strength. These studies indicate the involvement of cholinoceptive mechanisms in the elicitation of hypothalamically induced aggresive behaviour. Microinfustion of hexamethonium bromide, a nicotinic blocker in 50 micrograms doses did not affect the aggressive response.

A computer programme for recording male sex behaviour in rats.

An accurate method of recording the frequencies of copulatory events, the latencies of initiation to copulation and the time spent in different behavioural categories is described. A microcomputer (IBM-PC) based data collection system for acquisition and analysis of male rodent sex behaviour has been developed. This software features ease of data entry and operation, using single key presses by assigning a preset code to each. Internal clock of the computer is made to function as a timer for accurate recording of latencies and intervals. A print out of the frequency or duration of data can be obtained either concurrently or after the completion of the experiment, as required. The least count of the technique is about 10(-4) min and this precludes its use for extremely rapidly changing behaviour.

Midbrain adrenergic mechanisms modulating flight behaviour induced by hypothalamic stimulation.

The present study was carried out in ten cats of either sex. Flight response was obtained by electrical stimulation of dorsomedial regions of preoptic area (A13-14.5, L3.5 V-3.5 to -3.7) and lateral hypothalamic regions (A12.5, L2.5-3.5, V-3.7). It consisted of a goal directed attempt to get out of the cage with a vigorous leaping to foot. Norepinephrine when microinjected in 10 micrograms doses into pretectal area of midbrain (A3.5, 3.0, V+1.0 to +1.5 mm) significantly lowered the mean current strength from 640uA to 420uA; clonidine, an alpha-2 agonist in 5 micrograms dose when microinjected into the same locus also significantly lowered the mean current strength to the same level. On the other hand yohimbine, an alpha-2 blocker in 5 micrograms dose when microinjected in to the same locus significantly increased the mean current strength from 640 to 970 uA. These results indicate that hypothalamically induced flight response is mediated via the alpha-2 adrenoceptive mechanism operating at the midbrain level. Control microinjection of normal saline and propylene glycol in similar volumes failed to produce any changes in current strength.

Midbrain adrenergic mechanism modulating predatory attack behaviour induced by hypothalamic stimulation.

The present study was carried out in ten cats which did not attack the rats spontaneously. Predatory attack on a rat was produced by lateral hypothalamic stimulation using mean current strength of 340-690uA. This attack was accompanied by minimal affective display and culminated in neck biting. It was found that norepinephrine (NE) when microinjected into dorsal periaqueductal gray (dPAG) region in doses of 2, 4 and 10ug significantly lowered the mean current strength required for the elicitation of predatory attack by hypothalamic stimulation. Microinjection of propranolol (Prop), a beta-blocker, within the same region in similar doses significantly blocked the response as indicated by the increase in current strength required to produce the response. Control injections of normal saline and propylene glycol failed to produce any change. These findings indicate that hypothalamically induced aggressive responses involves beta adrenoceptive mechanisms located in the dPAG.

Role of opioid receptors in self-aggression in rats.

Self-aggression is a behavioural disorder in which an individual damages its own body parts by intense biting or scratching. Self aggression has been reported in human patients in Lesch-Nyhan syndrome and in cases of schizophrenia, depression, and congenital analgesia. In human patients as well as in experimental animals some kind of dysesthesia of the part of the body that is mutilated has been suggested. This study was conducted to find out the underlying pain mechanisms in self-aggressive behaviour arising out of stereotypy. The study was performed in 40 adult male rats. In all these animals, self-aggression was produced as part of amphetamine induced stereotyped behaviour. A predetermined scale was used for quantifying this behaviour. Reserpine and phenoxybenzamine pretreatment led to an increase in the incidence of self-aggression. Naloxone administration in reserpine pretreated animals led to a further significant increase in the incidence of self biting as compared to controls. From these studies it appears that self-aggressive behaviour may be associated with increased pain sensation.

Coitus induced changes in oviductal motility & effect of progesterone.

Motility of different oviductal segments of conscious rabbits was recorded through permanently implanted sensors using the technique of impedance plethysmography. The implants were around the oviductal wall and therefore did not obstruct its lumen. Pre-ovulatory ampullary motility was always less than the isthmic motility. Coitus induced ovulation produced a characteristic oviductal motility pattern consisting of (i) initial relaxation of both isthmus and ampulla (4-12 h) followed by (ii) increased isthmic motility in the face of a continually relaxed ampulla (36-48 h), and finally phase (iii) leading to restitution of both ampullary and isthmic motility to the base-line at 72-96 h. Estimation of ova positions indicated the presence of fertilized eggs in the ampulla and ampullo-isthmic junction at 48 h and the ova could come to the end of the isthmic segment only at 72 h or after. Increased isthmic motility thus served to counter the transportation of ova and their retention in the ampulla. Rabbits in which oviducts were not taken out for ova positioning achieved normal pregnancy. Administration of progesterone (im, 2.5 mg) produced complete relaxation of both isthmus and ampulla, did not produce increased isthmic contractility on coitus, accelerated the ovum transport rate and inhibited pregnancy, again emphasising the ova retentive role of oviductal motility.

Haemodynamic effects of hypothalamic stimulation on skin and muscle venous beds.

Twenty three points mainly located in the posterior hypothalamus were stimulated to study its effect on the pressures, flows and calculated segmental resistances of the skin and muscle venous beds of hind limbs in the dog. Stimulation of these points produced a uniform pattern of rise in pressures of the muscle veins consisting consisting of a steep rise during stimulation followed by a rapid decline to basal level on its cessation. Skin veins, on the other hand registered a gradual increase in pressure during stimulation followed by a secondary rise during post stimulatory period. Large veins of both muscle and skin exhibited comparatively smaller pressure increases than small vein. These pressure changes were accompanied by a similar marked rise in systemic arterial pressure. Out of 23 points, 21 points produced similar increases in the calculated resistances of skin and muscle veins. Two points produced greater increase of the skin vein resistance. Total venous resistance of the limb was therefore, raised by all the points stimulated. None of these points elicited any fall in the pressures or calculated resistances of either the muscle or skin venous bed. Muscle venous outflow always registered an increase while the skin venous outflow recorded either a small increase or decrease or at times no change during the hypothalamic stimulation. These findings demonstrate that hypothalamic stimulation can profoundly alter the haemodynamics of the hind limb venous beds and actively mobilize the post capillary venous sections of both skin and muscle venous beds.

Effect of luteinizing hormone-releasing hormone (LH-RH) on the multiunit activity of the arcuate nucleus in the proestrous rats.

Multiple Unit Activity (MUA) of the hypothalamic arcuate nucleus as indicated by discriminated spikes with window setting between 18-30 uV, the integrated MUA and the cortical EEG of the urethane anaesthetized rats on the proestrous day was recorded with the help of a polygraph. Infusion of LH-RH in the 3rd ventricle markedly increased the arcuate nucleus MUA. The effect started within minutes of infusion, peak came after 20-30 minutes and the activity remained increased for 3-4 hours. Saline infusion in the 3rd ventricle was ineffective. Feedback action of CSF-LH-RH to the arcuate nucleus for the regulation of LH-RH is suggested.

Central nervous control of venous tone. III. Responses of capacitance and resistance vessels of skin to bulbar and hypothalamic stimulation.

Electrical stimulation of 350 points in the bulbar formation of 35 dogs under chloralose anaesthesia demonstrated the presence of sites producing increase or decrease of systemic arterial pressure (SAP) in the same general morphological limits of bulbar pressor and depressor regions as described by earlier authors. Simultaneous recording of pressure changes in the cutaneous vessels however demonstrated that pressure changes in these vessels did not correspond to the pressor or depressor effects of the SAP. Instead, responses were obtained in which pressures in cutaneous capacitance and resistance vessels followed a trend which was opposite in direction and magnitude to that of SAP. Thus there were 30 depressor sites which produce increase in cutaneous vessel pressure and 23 pressor sites which produced a fall in cutaneous vessel pressure. For a marked rise in the SAP, only 62 sites elicited equally marked increase in both capacitance and resistance vessel pressure, while another 52 elicited only a small increase of equivalent magnitude in the capacitance and resistance vessels. Stimulation of 84 points produced dissimilar effects on capacitance and resistance vessels out of which 38 elicited moderate increase in resistance vessel tone with minimal changes in the capacitance vessel tone, while 46 points elicited moderate increase in capacitance vessel tone with only a small increase in the resistance vessel tone. These points were diffusely admixed in the bulbar reticular formation. Effects which were exclusive to the capacitance and resistance vessels of skin, singly or in combination, without affecting the SAP were elicited from 12 points while another 28 points produced marked rise or fall of systemic arterial pressure without affecting the cutaneous vessels. These observations suggest that the neuronal organisation regulating cardiovascular activities at the bulbar level is quite complex having the capacity to generate varying activities in different components of the vascular circuits by differentially altering the discharge of the efferent sympathetic fibres on the one hand, and marked selectivity of action on any particular vascular bed or circulatory component on the other hand. Stimulation of 93 points in the hypothalamus produced similar patterns of response as obtained from medulla oblongata. In addition, stimulation of 6 points in the anterior hypothalamus produced a distinctive response accompanied by dilatation of cutaneous resistance and capacitance vessels with marked increase in respiratory rate and minimal changes in the SAP. This type of response which resembled the physiological response employed for heat loss was not obtained from any stimulation site in the medulla oblongata.