Rôle of potassium and calcium in the turnover of acetylcholine.
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Biomedical subjects
Publications and source records attributed to T Desiraju.
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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.
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.
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.
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.
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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)
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