Dose-response functions of apomorphine, SKF 38393, LY 171555, haloperidol and clonidine on the self-stimulation evoked from lateral hypothalamus and ventral tegmentum.

The experimental animals were implanted with two bipolar electodes, one in the lateral hypothalamus including medial forebrain bundle (LH-MFB) and other in ipsilateral ventral tegmental area-substantia nigra (VTA-SN) and were trained to press a pedal for self-stimulation. This provided the scope to compare directly the effect of a given dose of a drug on the two reward regions in the same animal in the same testing situation. The current intensity was set to produce intracranial self-stimulation (ICSS) response rates of 50% less than the maximal shaping response rates for the respective animals (M60). Following systemic (intraperitoneal) administration of apomorphine (a dopamine receptor D1/D2 mixed agonist), SKF 38393 (D1 > D3 > D2 agonist), LY 17155 or quinpirole (D3 > D2 and D1) agonist), haloperidol (a DA-D2 antagonist), and clonidine (noradrenaline receptor alpha 2 agonist), the ICSS response rates evoked from LH-MFB and VTA-SN were compared with vehicle or saline-treated animals on the basis of dose-response functions. A dose-dependent inhibitory effect at M50 was observed with apomorphine (0.01-1.00 mg/kg) and haloperidol (0.05-0.30 mg/kg) for both the sites of stimulation. These doses of haloperidol did not produce any motor deficits like catalepsy and muscular rigidity. The dose-response and time-effect functions of SKF 38393 and LY 171555 at M50 showed the facilitation and suppression of ICSS of VTA-SN and LH-MFB respectively. Clonidine (0.05-0.25 mg/kg) also produced inhibitory effect on ICSS rates, but this suppression was of different magnitude with respect to the site of stimulation. These doses of clonidine were in the range that did not prevent active pedal pressing responses. ED50 (the dose required to reduce the ICSS response rate 50% of the rate after administration of vehicle) for LY 171555 was 0.8 and 4.4 mg/kg for the ICSS of VTA-SN and LH-MFB respectively and thus statistically different ED50 for apomorphine was 0.27 and 0.36 mg/kg; and for haloperidol was 0.75 and 0.90 mg/kg for LH-MFB and VTA-SN respectively and thus not different significantly. ED50 for clonidine was 0.25 and 0.08 mg/kg for VTA-SN and LH-MFB respectively and thus statistically different. The two-way analysis of variance (ANOVAR) of interaction of dose-response function of alpha 2 agonist with respect to LH-MFB and VTA-SN showed significant independence in their suppressive effects.

Plasticity of hippocampal and motor cortical pyramidal neurons induced by self-stimulation experience.

The self-stimulation (SS) induced neuronal plasticity was observed in CA3 hippocampal and layer V motor cortical pyramidal neurons. SS experience was allowed daily for a total of 1 hour for 10 days through four bipolar electrodes implanted bilaterally in lateral hypothalamus (LH) and substantia nigra-ventral tegmental area (SN-VTA) in adult male Wistar rats. Examination of pyramidal neurons stained by rapid Golgi technique was made in a total of 1,600 neurons out of 80 rats consisting of 4 groups. The dendritic intersections were quantified upto 200 and 120 microns radial distances in apical and basal dendrites respectively. The CA3 hippocampal and layer V motor cortical pyramidal neurons of SS group revealed significant increase (P < 0.001, two-way ANOVA) in dendritic intersections in both apical and basal dendrites, compared to normal control (NC), sham control (SH) and experimenter-administered (EA) group of animals. These results demonstrate that SS experience promotes increase in dendritic length in hippocampal and motor cortical pyramidal neurons.

Recording of auditory middle latency evoked potentials during the practice of meditation with the syllable 'OM'.

Middle latency auditory evoked potentials were examined in 7 proficient subjects during the practice of meditation on the syllable 'OM', to determine whether these potentials would differ significantly from those recorded during the baseline state without practicing mediation. Similar records were also obtained in 7 'naive' subjects, matched for age, before and during a control period which involved sitting with eyes closed, and with no special instructions for focusing their thoughts. There was considerable inter-subject variability in the different components. However, during meditation there was a small but significant reduction in the peak latency of the Nb wave (the maximum negativity occurring between 35 and 65 msec). This reduction was observed consistently during the 3 repeat sessions of each subject, while the 'naive' subjects did not show this change. These results suggest that the inter-subject variability of middle latency auditory evoked potentials precludes using them as the method of choice for assessing the effects of meditation. The small but consistent decrease in the Nb wave peak latency, indicates that the middle latency auditory evoked potentials do change with meditation. However, the variability of the potentials may mask subtle changes.

Physiological changes in sports teachers following 3 months of training in Yoga.

1. This report shows that in a group of 40 physical education teachers who already had an average of 8.9 years physical training, 3 months of yogic training produced significant improvement in general health (in terms of body weight and BP reduction and improved lung functions). 2. There was also evidence of decreased autonomic arousal and more of psychophysiological relaxation (heart rate and respiratory rate reduction), and improved somatic steadiness (decreased errors in the steadiness test). 3. The changes at the end of 3 months in volar GSR in different directions (increase/decrease/no change), depending on the initial values, suggests that practising yoga may help to bring about a balance in different autonomic functions, so that functioning is optimised.

EEG spectral power reduction and learning disability in rats exposed to lead through postnatal developing age.

The present study was carried out to assess electrophysiological and behavioral changes in Wistar rats caused by consuming a daily dose of lead acetate (400 micrograms lead/g body weight/day, given by gastric intubation, from second day of birth to 60 days of age. At 60 days of age, the lead treated rats showed in both wakeful and slow wave sleep stages, a statistically significant reduction in the delta, theta, alpha and beta band EEG spectral power in motor cortex (MC) and hippocampus (HI) with the exception of the delta and beta bands power of MC in wakeful state (WA). Lead administration was discontinued after that age for allowing rehabilitation for 40 days. Then, operant behavioral assessment was done. Results revealed that the lead treated animals took significantly more time and sessions than control normal animals in attaining criterion of learning. Hence exposure to lead in early age could result in a learning disability persisting even after discontinuation of exposure.

Oxygen consumption during pranayamic type of very slow-rate breathing.

To determine whether the yogic Ujjayi pranayamic type of breathing that involves sensory awareness and consciously controlled, extremely slow-rate breathing including at least a period of end-inspiration breath holding in each respiratory cycle would alter oxygen consumption or not, ten males with long standing experience in pranayama, and volunteering to participate in the laboratory study were assessed. These subjects aged 28-59 yr, had normal health appropriate to their age. Since kumbhak (timed breath holding) is considered as an important phase of the respiratory cycle in the pranayama, they were categorised into two groups of five each, one group practising the short kumbhak varieties of pranayama, and the other the long kumbhak varieties of pranayama. The duration of kumbhak phase was on an average 22.2 percent of the respiratory cycle in the short kumbhak group, and 50.4 per cent in the long kumbhak group. The oxygen consumption was measured in test sessions using the closed circuit method of breathing oxygen through the Benedict-Roth spirometer. Each subject was tested in several repeat sessions. Values of oxygen consumption of the period of pranayamic breathing, and of post-pranayamic breathing period, were compared to control value of oxygen consumption of the prepranayamic breathing period of each test session. The results revealed that the short kumbhak pranayamic breathing caused a statistically significant increase (52%) in the oxygen consumption (and metabolic rate) compared to the pre-pranayamic base-line period of breathing. In contrast to the above, the long kumbhak pranayamic breathing caused a statistically significant lowering (19% of the oxygen consumption (and metabolic rate).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of lesions of areas of brain--stimulation reward of one region of brain on operant behaviour for receiving electrical stimulation into sites of another region and on operant behaviour for food reward.

It was aimed to study the effects of lesions of a self-stimulation (SS) area of one region of brain on the SS of another region, and on feeding behaviour in adult Wistar rats (males). The two regions proposed for study were the lateral hypothalamus (LH) and the substantia nigra-ventral tegmental area (SN-VTA). The objective was to elucidate whether each region had its own neural organization for SS behaviour or not, and whether the neural substrates of SS behaviour and feeding behaviour were one, or separate. Four bipolar electrodes were implanted bilaterally in LH and SN-VTA in each rat, and their SS pedal press rates for rewarding electrical stimulations were characterised. The rats were also trained in operant conditioning paradigm for receiving reward of food grains in FR-30 schedule. Their free-field food intake in home cages was measured. Later, electrolytic lesions of the four electrode sites were made one after another at 2-day intervals through the same biopolar electrodes. After each lesioning, the SS of the same and of the other electrode sites, and the operant performance of FR-30 food reward schedule, and daily free-field food intake (in home cage) were determined. Lesions of the LH SS site always disrupted SS-of contralateral LH but not of SN-VTA SS. Lesions of SN-VTA had not modified contralateral SN-VTA SS. A study of effects of ipsilateral lesions of LH SS site on SN-VTA SS, or of lesions of SN-VTA SS site on LH SS, revealed a range of changes, as were also effects on the FR-30 operant performance and daily food intake. Medium size lesions of SS area made in one region affected the SS of that area but not usually the SS of the other region. Large lesions of one region affected the SS of the other regions also. With large lesions, feeding behaviour also was affected, firstly of the operant type and secondly the free-field type.

Comparative assessment of pedal pressing rates of self-stimulation of hypothalamus and midbrain with both square wave and sine wave stimulus parameters.

In Wistar rats, the regional differences of pedal pressing rates of self-stimulation (SS) of lateral hypothalamus (LH) and substantia nigra-ventral tegmental area (SN-VTA) were assessed with electrodes implanted in both regions in each subject. Average of SS rates of SN-VTA sites was significantly higher than that of LH sites, tested with both sine wave and square wave types of stimuli. There was no significant difference in SS rates between males and females, and also in the females between different days of oestrus cycles. The high rates of robust SS observed in this study relative to SS rates reported in past literature were probably due not only to the placements of electrodes in the main substrates of SS, but also to the parameters of stimulus used (0.25 sec trains of sine waves through bipolar electrodes).

Inhibition of positively rewarding behavior by the heightened aggressive state evoked either by pain-inducing stimulus or septal lesion.

Using a footshock elicited aggression paradigm, aggressive responses were scored in normal and in septal-lesioned adult male Wistar rats. Septal lesions were made electrolytically to include the medial and lateral septal nuclei. The lesion was confirmed by behavioral criteria (septal aggression) and post-mortem histology. The aggressive response types (threat, attack) of the septal animals were compared with their corresponding age and weight matched controls. Results showed a statistically significant increase (P = 0.05) in the number of attack responses but not the threat responses in septal animals. The modulatory role of the aggressive experience on responsiveness to positively rewarding or hedonic stimuli was assessed by quantifying the intracranial self-stimulation (SS) rates that were obtained before and after an aggression schedule. For testing the SS behavior bipolar electrodes were implanted in the ventral tegmental area--substantia nigra (VTA-SN). Results showed a decrease in SS pedal press rates in post-aggression schedule as compared to the pre-aggression period in the normal subjects. This depressing effect lasted for over a week. In septal lesioned rats the SS rates were virtually abolished even without having an aggressive schedule. These experiments revealed the effect of environment and of a brain area in provoking aggressive mood and its inhibitory consequence on responding for positive experience.

Investigation of influence of diazepam, valproate, cyproheptadine and cortisol on the rewarding ventral tegmental self-stimulation behaviour.

Experiments were carried on in the Wistar rats having self-stimulation (SS) electrodes implanted chronically in substantia nigra-ventral tegmental area (SN-VTA) to examine whether modulations of GABAergic, serotonergic, histaminergic, dopaminergic, and glucocorticoid neuronal receptor functions will affect or not the brain reward system and the SS behaviour. The modulators are the wellknown drugs: diazepam which is a facilitator of some of the GABA receptors, and used clinically for its tranquilizing, anxiolytic, sedative-hypnotic and anti-convulsant properties; sodium valproate which is known to enhance the GABA synapse function, and used clinically for its anti-convulsant property; haloperidol which is a dopaminergic receptor (D2) blocker, and clinically used for its anti-psychotic property; cyproheptadine which is both anti-histaminic and anti-serotonergic (blocks 5-HT2 receptor), used clinically for its antihistaminic and other beneficial properties; and hydrocortisone which is the stress-resisting glucocorticoid having direct effects on both brain and body cells, used clinically for the wide-ranging glucocorticoid therapeutic effects. The results revealed that systemic administration of these drugs, except haloperidol, caused no significant influence on the SS behaviour, thereby indicating that these nondopaminergic drugs have no effect on brain-reward system and also these categories of synaptic actions are not likely to be involved in the primary organization of the mechanisms of the brain-reward system.

Success of autonomic operant conditioning of heart rate without involving contractions of somatic skeletal muscles.

In conscious Wistar rats neuromuscularly paralysed by gallamine, operantly conditioned reduction of heart rate was achieved under both negative and positive reinforcement schedules using the tail shock avoidance or the rewarding brain-stimulations in 20-min test sessions. The primary aim was to assess whether it would be possible to achieve operant conditioning of the heart rate, evoked not as a secondary reflex response of any voluntary skeletal muscular contractions of trunk but as a conditioned voluntary function of the central autonomic regulation of a visceral organ, since this entire subject was peculiarly left in confusion by Miller (5, 8) who wanted that others should independently study it. This study revealed interestingly that not every subject might be able to achieve the visceral learning in a given set of conditions, and suggested that this type of a special learning might be dependent on individual predisposition in the central nervous system. In the present study, 15 showed the learning, out of the 58 subjects assessed. It was also observed that there was a variation in the magnitude of the learning response among different learners, and, also, in the same subject in different sessions conducted on different days. This is considered as an indication that this type of conditioned autonomic function is probably not easily recruited into the long-term memory mechanisms. The overall average of the operant lowering of the heart rate progressively achieved by the end part of the learning session was about 10.5% from the basal average rate, and the score of reinforcement (per cent of painful tail shocks avoided, or of increase in number of brain shocks achieved) was over 80%. The extinction test confirmed the learning. Control experiments revealed that the conditioned heart rate changes were not due to any unconditioned stimulus effects. The learning observed under the brain-stimulation reinforcement was confirmed by losing the learning response after lesioning the site of the rewarding stimulation. The visceral operant learning occurring in state of somatomotor paralysis under both negative and positive types of reinforcement was blocked by haloperidol. Morphine delayed the onset of the pain avoidance operant learning, whereas it speeded up the hedonic brain-stimulation operant learning. The results, considered from all the above angles, dispell the doubt previously expressed about the occurrence of the operant conditioning of heart rate under a visceral learning paradigm.

Effects of succinylcholine and related substances administered into the medial preoptic area on the local EEG, body temperature, heart rate, galvanic skin resistance and biogenic amines.

Succinylcholine (Sch) which is a cholinergic neuromuscular blocker has been known to occasionally lead to episodes of malignant hyperthermia in swine and humans. In order to find whether it produces any hyperthermic effects through action on medial preoptic area, experiments were carried on by administering intracerebrally the chemical into the medial preoptic area through an in-dwelling cannula-cum-electrode in the free moving rat. The changes in body temperature and the local EEG were studied. For comparison purpose, the effects of carbachol, atropine and phenylephrine were also studied. Further, in the curarized state of no muscular activity, the effect of SCh on the preoptic area was again tested and also the changes in the other autonomic parameters of heart rate and galvanic skin resistance (GSR) were studied. It was observed that SCh given into preoptic area caused a clear hyperthermic effect. The effect was countered by prior administration of atropine into the site. After SCh the local EEG changed into a high amplitude slow wave format. The heart rate was not altered but the GSR increased by two-fold. Carbachol caused a rise in body temperature, heart rate and also GSR. SCh also caused a reduction in noradrenaline content of the hypothalamus by 23% while no change in dopamine and serotonin occurred. Serotonin increased by 28% in the brainstem with no change in the other amines. Septum showed an increase of noradrenaline and dopamine contents by 40% and 25% respectively. Keeping in view the monoaminergic connections and thermoregulatory role of the preoptic area, one may postulate that SCh could inhibit the warm sensors and the controls of the dual sympathetic mechanism which normally leads to an increase of sudomotor activity and a decrease of vasomotor activity, the inhibition resulting in rise of body temperature.

Designing of a brain stimulator suitable for intracranial self-stimulation experiments for studying the brain-stimulation reward system.

A circuit design has been developed and described for fabricating and using in the intracranial self-stimulation experiments on rat to study the brain-stimulation reward behaviour, and to explore into the underlying mechanisms of drives and motivated behaviours. The stimulator can be fabricated with parts available in India. It has been continuously used and tested during the last four years in different research studies.

Experimental study on rats to find the usefulness of nutritional supplementation to undernourished offspring of parents undernourished life-long.

Undernourished parents getting only about half of normal feed requirement and whose body weights were deficient by 40-65% were mated and out of the resulting litters, the medium size (about 8) ones were culled to 8 per dam whose food supply was restricted to 10 g per day during the suckling (category M2). Another category (M3) was constituted out of large (over 12) litters born to similar undernourished parents and culling the litter size to 15 per dam besides restricting the dam's food to only 10 g per day during first week and to 15 g per day during the second and third weeks of suckling. Another category (M1) was constituted like M3 except that the parents were provided with normal, ad libitum nutrition throughout. Effects of post-weaning continuation of undernutrition or of rehabilitation with ad libitum food were studied in M2 groups of pups till 425 days of age. Further, an additional protein-deficient type of undernutrition (M4) was also superimposed in one group of M2 category of pups between day 41 and 60 of age, and then rehabilitated on to normal diet to find the additional effect of this additional load of the protein-malnutrition. The control groups of normal pups were also reared along with the above groups for comparisons. The normal diet had: 22.8% protein, 10.6% fat, 61% carbohydrate, and vitamins and minerals. By 21 days of age, the deficiencies of the M1, M2 and M3 were about 28%, 64% and 77% respectively in body weights, and about 8%, 21% and 30% respectively in brain weights. Continuing the undernutrition after weaning on half of normal feed, the M2 group of males and females stabilized at about 41% and 62% respectively of normal body weights by about 150 days of age. Rehabilitation of M2 or M4 groups by providing ad libitum feed had never recovered their pre-rehabilitation body weight deficits even after the ad libitum feeding for as long as 425 days of age. On the contrary, the brain weights seemed to have partially recovered from the earlier deficits, but here also the general conclusion of permanency of deficits stood unequivocally. The present study affirms that different degrees of gestational, lactational and post-weaning undernutrition can lead to different degrees of growth deficits and that supplemental feeding regimens introduced afterwards cannot bring out recoveries from such previous deficits which seem to remain permanently.(ABSTRACT TRUNCATED AT 400 WORDS)