Dopamine receptor sub-types involvement in nucleus accumbens and ventral tegmentum but not in medial prefrontal cortex: on self-stimulation of lateral hypothalamus and ventral mesencephalon.

The involvement of different sub-types of dopamine receptors in the electrical self-stimulation behaviour was investigated using DA receptor subtype specific agonists viz R(+) SKF 38393 and LY 171555 (quinipirole). Rats were chronically implanted with bipolar electrodes in lateral hypothalamus-medial forebrain bundles (LH-MFB) and ventral tegmental area-substantia nigra (VTA-SN) or guide cannula in nucleus accumbens (nACB) or medial prefrontal cortex (mPFRCx) or cannula-cum-electrode in VTA-SN. Combining these, it was possible to inject a given receptor ligand in either nACB or mPFRCx or VTA-SN and assess the changes in intracranial self-stimulation (ICSS) of LH-MFB or VTA-SN. The experimental subjects were trained to press a pedal to obtain 0.25 s trains of cathodal rectangular pulses of 0.1 ms pulse duration (for LH-MFB electrode) or 0.3 ms pulse duration (for VTA-SN electrode). The rate-frequency curve for each subject and each placement were obtained in order to determine M50 (50% of maximum asymptotic response rate). Microinjection of SKF 38393 (a D1 agonist) or LY 171555 (a D2 agonist) into nACB caused facilitatory and suppressive effects on the ICSS of VTA-SN and LH-MFB respectively. On the contrary, intra VTA-SN injection of 10 micrograms/0.5 microliter of SKF 38393 or of LY 171555, reduced its ICSS to half as compared to vehicle injections. Under the effect of these injections, there was no change in the ICSS of LH-MFB. The combined administration of SKF 38393 (5 micrograms) and LY 171555 (10 micrograms) into nACB produced suppression of ICSS of VTA-SN to greater extent than the LY 171555 (10 micrograms/0.5 microliter). This indicates that coactivation of D1 and D2 leads to suppression of ICSS of VTA-SN. The activation of D1 receptors in nACB facilitates the ICSS of both VTA-SN and LH-MFB by increasing the reinforcement and/locomotor activity, while the activation of D2 receptors in it has opposite effect. The coactivation of D1 and D2 receptors in VTA-SN leads to the suppression of ICSS of both VTA-SN and LH-MFB. Similar injections of these receptor ligands into mPFRCx did not alter the ICSS of either LH-MFB or VTA-SN. The pre- or post-synaptic DA receptors of mPFRCx do not appear to influence the ICSS of either VTA-SN or LH-MFB in any significant manner.

Cholinergic and GABAergic modulation of self-stimulation of lateral hypothalamus and ventral tegmentum: effects of carbachol, atropine, bicuculline, and picrotoxin.

This study aimed at investigating the effects of modulators of acetylcholine-muscarinic (ACh-M) and GABAA.B-receptors in the lateral hypothalamus and ventral tegmentum on the electrical self-stimulation evoked from these regions. In each Wistar rat, a bipolar electrode and an ipsilateral insulated cannula-cum-electrode were implanted chronically in the right hemisphere. There were two placement combinations: 1. Bipolar electrode in lateral hypothalamus-medial forebrain bundle (LH-MFB) and cannulacum-electrode in ventral tegmental area-substantia nigra (VTA-SN) or 2, bipolar electrode in VTA-SN and cannula-cum-electrode in LH-MFB. The stimulation parameters were kept at a level to obtain 50% of the maximum possible asymptotic intracranial self-stimulation (ICSS) rates (M50) from each site. Carbachol injected into VTA-SN increased the ICSS responding rate of VTA-SN as well as, indirectly, that of LH-MFB, and atropine injections had an opposite effect. Similar injections of these ligands into LH-MFB again had facilitatory and inhibitory effects on its ICSS: however, there was no indirect effect on the ICSS of VTA-SN. Bicuculline injection into VTA-SN had no effect on either its ICSS or that of LH-MFB. On the other hand, bicuculline injected into LH-MFB decreased its ICSS and, indirectly, the ICSS of VTA-SN in a dose-dependent manner. In contrast, intra VTA-SN injections of picrotoxin decreased its ICSS and, indirectly, ICSS of LH-MFB. Similar injections into LH-MFB had no effect on the ICSS of VTA-SN. The results suggest that ICSS of VTA-SN is Ach-M receptor mediated and, also, this mediation influences the ICSS of LH-MFB. On the contrary, changes in ICSS of LH-MFB following Ach-M receptor ligands do not influence the ICSS of VTA-SN. The direct effects of GABA-receptor antagonists have shown disassociation because ICSS of LH-MFB was more sensitive to bicuculline, whereas the ICSS of VTA-SN was more sensitive to picrotoxin. Thus, the cholinergic and GABAergic mechanisms of the self-stimulation of lateral hypothalamus and ventral tegmentum are different.

Effects of microinjections of cholecystokinin and neurotensin into lateral hypothalamus and ventral mesencephalon on intracranial self-stimulation.

Changes in intracranial self-stimulation (ICSS) evoked from ventral tegmental area-substantia nigra (VTA-SN) and lateral hypothalamus-medial forebrain bundle (LH-MFB) before and after microinjections of sulfated cholecystokinin octapeptide (CCK-8S) and unsulfated cholecystokinin (CCK-8US), neurotensin tridecapeptide ([D-Tyr11]NT(1-13) or [DTrp11]NT(1-13)) into either VTA-SN or LH-MFB were assessed. The current intensity was fixed at a level to obtain 60-70% of the maximal asymptotic rate. CCK-8S (0.10 microg/0.5 microl and 0.25 microg/0.5 microl) into VTA-SN resulted in dose-dependent decreases in VTA-SN ICSS of 38-42% and 78-92%, respectively, without affecting the ICSS of LH-MFB. Similar doses of CCK-8S injected into LH-MFB changed neither LH-MFB ICSS nor VTA-SN ICSS. CCK-8Us injected into VTA-SN or LH-MFB had no effect on ICSS in either site. Intra-VTA-SN injections of the neurotensin-1 (NT1) receptor agonist [DTyr11]NT(1-13) and the NT1 receptor antagonist [D-Trp11]NT(1-13) at doses of 5 microg/0.5 microl and 10 microg/0.5 microl decreased VTA-SN ICSS. NT1 receptor agonist and antagonist injections did not alter LH-MFB ICSS in any significant manner. Similar injections of these peptides into LH-MFB did not change the responding rates for LH-MFB ICSS or VTA-SN ICSS. Increasing the current intensity reversed the inhibitory effect of CCK-8S and [D-Trp11]NT(1-13) on VTA-SN ICSS and restored basal preinjection rates of responding. These results suggest that CCK(A) and NT1 receptor mechanisms in the ventral tegmentum in association with dopamine neurotransmission may be important in mediating the rewarding effects of VTA-SN ICSS but not LH-MFB ICSS.

Comparison of intracranial self-stimulation evoked from lateral hypothalamus and ventral tegmentum: analysis based on stimulation parameters and behavioural response characteristics.

The comparison of intracranial self-stimulation (ICSS) derived across the anteroposterior axis of medial forebrain bundle (MFB) from the anterior border of lateral hypothalamus (LH) to the ventral mesencephalon including ventral tegmental area-substantia nigra (VTA-SN) in Wistar rats was assessed through stimulation parameters and behavioural response characteristics. The interpretation of response rate/charge consumption (muC/min) with respect to rectangular wave and sine wave electrical stimulation parameters suggests that the rectangular wave parameters are better in order to get the maximum responding rates. The most vigorous and robust responding was observed in the VTA or VTA-SN boundary placements, followed by placements in medial sector of LH. The acquisition of ICSS was fastest in the case of VTA-stimulation. The next site with respect to rapidity of ICSS was posterio-ventral LH. The extinction curves indicated that it is faster and exponential in case of VTA-SN, but it is slower with longer duration in case of LH-MFB. ICSS of SN were accompanied by exploratory locomotion and head bobbing. Thirty-one percent subjects with SN/VTA stimulation showed rotational behaviour. Seventy-eight percent of subjects with LH stimulations showed stimulus-bound ejaculations. Thirty-two percent of subjects with posterior LH stimulations showed biting of pedal edges. LH stimulations were accompanied by induced seizures and increased grooming in 18% and 13% of subjects, respectively. There was lateralisation of cerebral hemispheric function as right paw preference was noted in majority of rats, whether sites of stimulation were in the left or right cerebral hemisphere. The various other modes of pedal pressing operants like use of paw and mouth, alternate paw dribbling, use of head electrode assembly to manipulate the pedal were also recorded and analysed.

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.

Alterations in auditory middle latency evoked potentials during meditation on a meaningful symbol--"Om".

Middle latency auditory evoked potentials were recorded in 18 male volunteers with ages between 25 and 45 years, 9 of whom had more than 10 years of experience in "Om" meditation (senior subjects), whereas the other 9 had no meditation experience (naive subjects). Both groups were studied in two types of sessions. (1) Before, during, and after 20 minutes of mentally repeating "one" (control session), and (2) a similar session, though with 20 minutes of mentally chanting "Om" (meditation session). The senior subjects showed a statistically significant (paired t-test) increase in the peak amplitude of Na wave (the maximum negative peak between 14 and 18 ms) during meditation, while the same subjects showed a statistically significant reduction in the Na wave peak amplitude during control sessions. In contrast, the naive subjects had a significant decrease in the Na wave peak amplitude during meditation sessions and a nonsignificant trend of reduction during control sessions, as well. This difference between senior and naive subjects was significant (two-way ANOVA). There were no significant changes in short latency wave V or Pa wave (the positive peak between the Na wave and 35 ms). The changes in the Na wave suggest that both mediation on a meaningful symbol, and mental repetition of a neutral word cause neural changes at the same level (possibly diencephalic). However, the change could be in opposite directions, and this difference could be correlated with differences in the duration of experience in meditation between senior and naive subjects.

Effects on operant learning and brain acetylcholine esterase activity in rats following chronic inorganic arsenic intake.

1. Very young and adult Wistar rats were given As5+, 5 mg arsenic kg-1 body weight day-1 (sodium arsenate). 2. Operant learning was tested in a Skinner box at the end of exposure and, in the case of developing animals, also after a recovery period. 3. Acetylcholine esterase (AChE) activity was estimated in discrete brain regions of these animals. 4. The animals exposed to arsenic took longer to acquire the learned behaviour and to extinguish the operant. AChE activity was inhibited in some regions of the brain.

Facilitation of self-stimulation of ventral tegmentum by microinjection of opioid receptor subtype agonists.

Intracranial self-stimulation (ICSS) evoked from the ventral tegmental area-substantia nigra (VTA-SN) and lateral hypothalamus-medial forebrain bundle (LH-MFB) was assessed following microinjections of mu (Tyr-D-Ala2-N-Me-Phe4-Gly5ol: DAGO), delta-(D-Ala2, D-Met5)-enkephalin: DADME) or kappa (Dynorphin-B or Rimorphin) opioid receptor subtype agonists or saline into either VTA-SN or LH-MFB. The current intensity was fixed at an optimum level to obtain 60-70% of the maximum asymptotic response rate. DAGO (5 micrograms/0.5 microliters), DADME (2 micrograms/0.5 microliters) or Dynorphin B (0.5 microgram/0.5 microliters) injected into VTA-SN facilitated the self-stimulation rates of VTA-SN by 27%, 32%, and 59%, respectively. These microinjections did not alter the self-stimulation of LH-MFB when effects of these injections were still persisting in VTA-SN. Similar doses of these opioid receptor agonists injected into LH-MFB had no significant effect on the self-stimulation rates of either LH-MFB or VTA-SN. The facilitatory effects of DADME were completely abolished by naloxone (30 mg/kg IP). Taken together, these results suggest that all three opioid receptor subtypes of ventral tegmentum and not of lateral hypothalamus are involved in the electrically evoked self-stimulation of VTA-SN.

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.

Neuronal plasticity induced by self-stimulation rewarding experience in rats--a study on alteration in dendritic branching in pyramidal neurons of hippocampus and motor cortex.

Self-stimulation rewarding experience promoted structural changes in pyramidal neurons of the CA3 region of the hippocampus and the Vth layer of the motor cortex in adult male Wistar rats. Self-stimulation experience was allowed for 1 h daily for a duration of 10 days through bipolar electrodes placed bilaterally in lateral hypothalamus and substantia nigra--ventral tegmental area. At the end of 10 days, rats were sacrificed, and rapid Golgi examination of the CA3 hippocampal and layer V pyramidal neurons of the motor cortex was made for a grand total of 1600 neurons from 80 rats divided into 4 groups. The neurons of the self-stimulation experienced (SS) group revealed a significant (ANOVA, F-test) increase in dendritic branching in the perisomatic domains. Such changes were not observed in neurons of sham control (SH), experimenter administered stimulation (EA) and normal control (NC) groups. SS animals also showed a significant increase in the thickness of lacunosum and radiatum laminae of CA3 neurons of the hippocampus. Our results reveal that both limbic and neocortical neurons undergo changes in dendritic branching patterns due to self-stimulation rewarding experience. It is tempting to hypothesize that neuronal plasticity is the result of motivation and learning experienced by rats which underwent self-stimulation.

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.

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.

Autonomic changes in Brahmakumaris Raja yoga meditation.

This report presents the changes in various autonomic and respiratory variables during the practice of Brahmakumaris Raja yoga meditation. This practice requires considerable commitment and involves concentrated thinking. 18 males in the age range of 20 to 52 years (mean 34.1 +/- 8.1), with 5-25 years experience in mediation (mean 10.1 +/- 6.2), participated in the study. Each subject was assessed in three test sessions which included a period of meditation, and also in three control (non-mediation) sessions, which included a period of random thinking. Group analysis showed that the heart rate during the meditation period was increased compared to the preceding baseline period, as well as compared to the value during the non-meditation period of control sessions. In contrast to the change in the heart rate, there was no significant change during meditation, for the group as a whole, in palmar GSR, finger plethysmogram amplitude, and respiratory rate. On an individual basis, changes which met the following criteria were noted: (1), changes which were greater during meditation (compared to its preceding baseline) than changes during post meditation or non-meditation periods (also compared to their preceding baseline); (2), Changes which occurred consistently during the three repeat sessions of a subject and (3), changes which exceeded arbitrarily-chosen cut-off points (described at length below). This individual level analysis revealed that changes in autonomic variables suggestive of both activation and relaxation occurred simultaneously in different subdivisions of the autonomic nervous system in a subject. Apart from this, there were differences in patterns of change among the subjects who practised the same meditation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations of auditory middle latency evoked potentials during yogic consciously regulated breathing and attentive state of mind.

Middle latency auditory-evoked potentials (AEP-MLRs) of 10 healthy male subjects in the age range of 21-33 years, were assessed to determine whether yogic pranayamic practice would cause changes in them. The pranayama type assessed here is an exercise of consciously-controlled rhythmic breathing involving timed breath-holding in each cycle of breathing, while the subject holds utmost attention and experiences the touch of inhaled air in the nasal passage. The results revealed that the Na-wave amplitude increased and latency decreased during the period of pranayamic practice, whereas the Pa-wave was not significantly altered. The change is interpreted as an indication of a generalized alteration cause in information processing at the primary thalamo-cortical level during the concentrated mental exercise of inducing modifications in neural mechanisms regulating a different functional system (respiratory). Further researches are required to understand the operational significances of such changes.

Mercuric chloride-induced alterations of levels of noradrenaline, dopamine, serotonin and acetylcholine esterase activity in different regions of rat brain during postnatal development.

Wistar rats were fed mercuric chloride, 4 mg/kg body weight per day chronically from postnatal day 2 to 60 by gastric intubation. Mercury consumption was then discontinued until 170 days to allow time for recovery. Since mercury caused reduction in body weight, an underweight group was also included besides the normal saline group. Levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and the activity of acetylcholine esterase (AChE) were assayed in various brain regions in different age groups. By 60 days of age, the mercury group showed elevations of NA levels in olfactory bulb (OB), visual cortex (VC) and brain stem (BS) but not in striatum-accumbens (SA) and hippocampus (HI). DA levels were also increased in OB, HI, VC and BS but not in SA. AChE activity was decreased in the mercury group only in HI and VC at 20 days of age. The Mercury group showed no behavioural abnormality outwardly; however, operant conditioning revealed a deficiency in performance. Nevertheless, all these changes disappeared after discontinuation of mercury intake. Thus the changes occurring in the brain at this level of oral mercuric chloride intake seem to reflect adaptive neural mechanisms rather than pathological damage.

Effects of chronic consumption of metanil yellow by developing and adult rats on brain regional levels of noradrenaline, dopamine and serotonin, on acetylcholine esterase activity and on operant conditioning.

Metanil yellow is the principal non-permitted food colour used extensively in India. The effects of long-term consumption of metanil yellow on the developing and adult brain were studied using Wistar rats. Regional levels of noradrenaline, dopamine and serotonin, activity of acetylcholine esterase (AChE), and operant conditioning with food reward were assessed in rats fed, metanil yellow and in controls. In the treated rats the amine levels in the hypothalamus, striatum and brain stem were significantly affected, and the changes were not generally reversible even after withdrawal of metanil yellow in developing rats. The striatum showed an early reduction of AChE activity, whereas the hippocampus showed a delayed but persistent effect of reduced AChE activity. Treated rats also took more sessions to learn the operant conditioning behaviour. These effects on these major neurotransmitter systems and on learning, indicate that chronic consumption of metanil yellow can predispose both the developing and the adult central nervous system (CNS) of the rat to neurotoxicity.

Effect of chronic consumption of methylparathion on rat brain regional acetylcholinesterase activity and on levels of biogenic amines.

Wistar rat pups (female) were exposed to methylparathion (MPTH) by gastric intubation in single doses, or in a chronic regimen of different durations. A single dose of 1 mg MPTH/kg body weight in 15-day-old pups caused a significant decrease of acetylcholinesterase (AChE) activity in cerebellum (CE), motor cortex (MC) and brain stem (BS). The effect began to appear in about 20 min after administration, the peak effect was attained in 120 min and later on this waned off completely by 24 h. The effect was similar in young (15 days) and in adult (70 days) rats. A single dose of 0.2 mg MPTH/kg in 15 day old pups caused a reduction of AChE activity only in the BS, while a 0.1 mg MPTH/kg single dose given to 15-day-old pups caused no effect even in seven regions of the brain examined. Effect of low dose chronic administration of MPTH on AChE activity was also studied in CE, MC, BS, hippocampus (HI), striatum-accumbens (SA), spinal cord (SC) and also in the hypothalamus (HY). Administration of 0.1 mg MPTH/kg from second day to 15 days of age caused significant reduction of AChE activity in only 2 of the 7 brain regions studied. Administration of double the dose (0.2 mg MPTH/kg) and for a longer duration (2nd day to 150 days of age), caused a depression in all the brain regions studied. In all these regions, the levels of NA, DA and 5HT did practically not change. The results suggest that chronic consumption of MPTH leads to a moderate decrease of AChE activity in several brain regions.