Role of sound stimulation in reprogramming brain connectivity.

Sensory stimulation has a critical role to play in the development of an individual. Environmental factors tend to modify the inputs received by the sensory pathway. The developing brain is most vulnerable to these alterations and interacts with the environment to modify its neural circuitry. In addition to other sensory stimuli, auditory stimulation can also act as external stimuli to provide enrichment during the perinatal period. There is evidence that suggests that enriched environment in the form of auditory stimulation can play a substantial role in modulating plasticity during the prenatal period. This review focuses on the emerging role of prenatal auditory stimulation in the development of higher brain functions such as learning and memory in birds and mammals. The molecular mechanisms of various changes in the hippocampus following sound stimulation to effect neurogenesis, learning and memory are described. Sound stimulation can also modify neural connectivity in the early postnatal life to enhance higher cognitive function or even repair the secondary damages in various neurological and psychiatric disorders. Thus, it becomes imperative to examine in detail the possible ameliorating effects of prenatal sound stimulation in existing animal models of various psychiatric disorders, such as autism.

Nimodipine is more effective than nifedipine in attenuating morphine tolerance on chronic co-administration in the rat tail-flick test.

Opioids, when co-administered with L-type calcium channel blockers (L-CCBs) show morphine like higher antinociceptive effect. This antinociceptive effect has been further investigated using a different experimental paradigm. The effect of two different L-CCBs (nifedipine and nimodipine) on morphine-induced antinociception was studied by the tail-flick test (40 min after morphine administration) in adult Wistar rats. A fixed-dose of nimodipine or nifedipine (2 mg/kg, once daily) was combined with a fixed dose of morphine (10 mg/kg, twice daily) for 10 days. Co-administration of L-CCBs significantly increased the antinociceptive effect of morphine, even 12 hr after administration. Also, nimodipine was more effective than nifedipine. Nimodipine was further studied using a higher and escalating doses of morphine (20-30 mg/kg twice daily for 14 days). Nimodipine increased the antinociceptive effect of morphine in the latter part of the study (days nine to fourteen) though significant difference was observed on 11th evening and 12th morning. No obvious adverse effects were observed in the present study. The results show for the first time that nimodipine is more effective than nifedipine and that these L-CCBs continue to be effective, even 12 hr after administration in the tail-flick test.

Enhanced analgesic effect of morphine-nimodipine combination after intraspinal administration as compared to systemic administration in mice.

Calcium plays an important role in the pathophysiology of pain. A number of studies have investigated the effect of L-type calcium channel blockers on the analgesic response of morphine. However, the results are conflicting. In the present study, the antinociceptive effect of morphine (2.5 microg) and nimodipine (1 microg) co-administered intraspinally in mice was observed using the tail flick test. It was compared to the analgesic effect of these drugs (morphine - 250 microg subcutaneously; nimodipine - 100 microg intraperitoneally) after systemic administration. Nimodipine is highly lipophilic and readily crosses the blood brain barrier. Addition of nimodipine to morphine potentiated the analgesic response of the latter when administered through the intraspinal route but not when administered through systemic route. It may be due to direct inhibitory effect of morphine and nimodipine on neurons of superficial laminae of the spinal cord after binding to mu -opioid receptors and L-type calcium channels respectively.

Acute analgesic effect of loperamide as compared to morphine after intrathecal administration in rat.

Loperamide, a mu opioid receptor agonist, which is commonly used as an antidiarrhoeal agent has been reported to possess analgesic activity after intrathecal administration. However, the exact analgesic profile, i.e., onset, duration and intensity of analgesia in relation to morphine is not fully known. In the present study, the acute analgesic effect of loperamide (5 microg) was compared with that of morphine (5 microg) and morphine + loperamide (5 microg of each) using the tail flick method after intrathecal administration. Naloxone (5 mg/kg) reversibility of the analgesic effect was also studied. The analgesic response of loperamide was significantly higher than morphine. Even after 22 hr, maximum possible effect was greater than 49%. Naloxone partially antagonized the analgesic effect of loperamide. This suggested that loperamide may be acting through blockade of Ca2+ channels besides activating mu opioid receptors. Loperamide may prove to be a better substitute for morphine as spinal analgesic.

Expression of opioid receptor-like 1 (ORL1) & mu opioid receptors in the spinal cord of morphine tolerant mice.

BACKGROUND & OBJECTIVE: The mechanism underlying the development of tolerance to morphine is not clearly understood though a number of factors have been implicated. One of the likely factors may be increased activity of anti-opioid peptides like nociceptin (also known as orphanin FQ or N/OFQ). N/OFQ and morphine bind to opioid receptor-like 1 (ORL1) receptor and muopioid receptor respectively. The present work was undertaken to investigate the density of ORL1 and mu (mu) receptor expression in the spinal cord of mice after inducing morphine tolerance. METHODS: Swiss albino mice were injected with either morphine (experimental group, n=15) or saline (control, n=15), twice a day for 9 days. The development of tolerance was noted by the hotplate test. Cryostat sections of the cervical region of spinal cord were labeled with specific ligands to localize ORL1 and mu receptors. The density of receptor expression over laminae I-II of spinal cord was evaluated using image analysis system. RESULTS: The morphine treated mice developed tolerance by day 9 as evident by the hot plate test. Both receptors were selectively expressed at a higher concentration over the superficial laminae (I-II) of the dorsal horn, indicating a role in pain processing. An increased expression of ORL1 receptors was also noted over the gray matter around the central canal. Quantitative analysis showed an increased expression of ORL1 and mu receptors though the increase was not statistically significant. INTERPRETATION & CONCLUSION: The present study showed that both, ORL1 and mu-opioid receptors were expressed in areas of the spinal cord, concerned with transmission of pain signals. The density of these receptors increased in the superficial laminae (I-II) though not significantly from control after morphine tolerance. The increase in ORL1 receptors could oppose the analgesic action of morphine, contributing to tolerance. Further studies need to be done to elucidate the mechanism of morphine tolerance.

Expression of mu-opioid receptors in developing rat spinal cord: an autoradiographic study.

The expression of mu-opioid receptors in the developing rat spinal cord (Postnatal days 7, 14, 30) was studied by autoradiography using [3H]DAMGO. When compared to camera lucida drawings, the receptor was noted over the entire gray matter and dorsal root ganglia at postnatal days 7 and 14. At postnatal day 30, the receptor expression decreased over the gray matter except the superficial laminae (laminae I and II). At all age groups studied, a higher expression of the receptor was noted over the superficial laminae. The study shows that micro-opioid receptors appears early in postnatal development and attains mature receptor distribution relatively late in ontogeny, suggesting a possible role in the normal development of nervous system. This is affirmed by an impairment of psychomotor development in babies born to mothers, addicted to opiates.

Effect of prenatal species-specific and music stimulation on the postnatal auditory preference of domestic chick.

Perinatal sensory experience plays an important role in the development of perceptual preferences. In the present study prenatal enrichment with sound stimulus was given to see its effect on the development of postnatal auditory preference. Auditory stimulation with either species-specific (chicken maternal and hatching calls) or music (slow and fast sitar music) sounds was provided to two separate sets of fertilized eggs from the day 10 of incubation. The postnatal auditory preference of the chicks to either species-specific or music sounds was then tested at different time periods after hatching. All the chicks, irrespective of the type of prenatal exposure, showed preference for species-specific maternal calls. Notably, the music stimulated chicks did not show preference for either slow or fast music. In both the experimental groups, the number of chicks responding to the species-specific maternal calls was significantly (P<0.001) more at 24 h and 48 h post hatch, when compared with the unstimulated control group. Comparison of the species-specific stimulated group with the music stimulated group, for auditory preference to the maternal calls, did not show any significant difference. Further, in the species-specific sound stimulated groups, there was a significant (P<0.001) increase in the number of chicks responding to maternal calls at 60 h of age with repeated testing. However, there was no effect of peer imprinting on the auditory preference of the chicks, in both the experimental groups. The results indicate that prenatal auditory experience with either species-specific or non-specific music enhances the postnatal auditory preference of chicks for the species-specific sounds.

Expression of the neurotrophin receptors Trk A and Trk B in adult human astrocytoma and glioblastoma.

Neurotrophins and their receptors of the Trk family play a critical role in proliferation, differentiation and survival of the developing neurons. There are reports on their expression in neoplasms too, namely, the primitive neuroectodermal tumours of childhood, and in adult astrocytic gliomas. The involvement of Trk receptors in tumour pathogenesis, if any, is not known. With this end in view, the present study has examined 10 tumour biopsy samples (identified as astrocytoma, pilocytic astrocytoma and glioblastoma) and peritumoral brain tissue of adult patients, for the presence of Trk A and Trk B receptors, by immunohistochemistry. The nature of the tumour samples was also confirmed by their immunoreactivity (IR) to glial fibrillary acidic protein. In the peritumoral brain tissue, only neurons showed IR for Trk A and Trk B. On the contrary, in the tumour sections, the IR to both receptors was localized in the vast majority of glia and capillary endothelium. There was an obvious pattern of IR in these gliomas: high levels of IR were present in the low-grade (type I and II) astrocytoma; whereas in the advanced malignant forms (WHO grade IV giant cell glioblastoma and glioblastoma multiforme) the IR was very weak. These findings suggest that Trk A and Trk B are involved in tumour pathogenesis, especially in the early stage, and may respond to signals that elicit glial proliferation, and thus contribute to progression towards malignancy.

Training of postgraduates in anatomy.

It is recognized that training methods differ among the various medical colleges; however, trained specialists should be competent to discharge their duties independently in any part of the country. Therefore, to maintain uniform standards of education, there is a need to harmonize postgraduate training in anatomy. It is proposed that a structured training programme should be drawn up and monitored regularly at specified intervals, spelling out some clearly defined targets that need to be achieved. The ultimate goal of the postgraduate training programme should be to produce anatomists with sufficient knowledge and practical skills to undertake undergraduate teaching and evaluation in all branches of anatomy, as well as to pursue research independently.

Immunohistochemical analysis of glutamate, cholecystokinin and vasoactive intestinal polypeptide in the lateral geniculate complex of albino rat: A developmental study.

The lateral geniculate nuclear complex of albino rats was investigated with respect to the development of neurotransmitters/neuromodulators such as glutamate, cholecystokinin and vasoactive intestinal polypeptide at gestational day 18, various postnatal age periods and in the adult using immunohistochemical methods. The study shows the unequivocal presence of and the sequential changes in the profile of glutamate while cholecystokinin and vasoactive intestinal polypeptide are not demonstrable at any of the age periods. Glutamate is seen both in the cells and fibres from 40 postnatal day onwards and immunoreactivity is more intense in the adult. The findings are discussed with relevance to the role of neurotransmitters in development.