Electrophysiological alterations in a complex rat model of schizophrenia.

BACKGROUND: Psychiatric disorders are frequently accompanied by changes in brain electrical oscillations and abnormal auditory event related potentials. The goal of this study was to characterize these parameters of a new rat substrain showing several alterations related to schizophrenia. METHODS: Male rats of the new substrain, developed by selective breeding after combined subchronic ketamine treatment and postweaning social isolation, and naive Wistar ones group-housed without any interventions were involved in the present study. At the age of 3 months, animals were implanted with cortical electroencephalography electrodes. Auditory evoked potentials during paired-click stimuli and power of oscillation in different frequency bands were determined with and without acute ketamine (20mg/kg) treatment. RESULTS: Regarding the auditory evoked potentials, the latency of P2 was delayed and the amplitude of N1 peak was lower in the new substrain. The new substrain showed increased power of oscillations in the theta, alpha and beta bands, while decreased power was detected in delta and gamma2 bands (52-70Hz) compared with control animals. Acute ketamine treatment increased the gamma1 band (30-48Hz) power in both groups, while it elicited significant changes only in the new substrain in the total power and in alpha, beta and gamma2 bands. CONCLUSIONS: The validation of the translational utility of this new rat substrain by electrophysiological investigations revealed that these rats show abnormalities that may model a part of the neurophysiological deficits observed in schizophrenia.

Characterization of gene-environment interactions by behavioral profiling of selectively bred rats: the effect of NMDA receptor inhibition and social isolation.

Gene-environment interactions have an important role in the development of psychiatric disorders. To generate and validate a new substrain of rats with signs related to schizophrenia, we used selective breeding after postweaning social isolation and chronic ketamine treatment through several generations of animals and compared the subsequent strain to naive rats that were not genetically manipulated. We further investigated whether social isolation and ketamine treatment augmented the appearance of schizophrenic-like signs in these rats. Four experimental groups were studied (n=6-15 rats/group): naive rats without any treatment (NaNo); naive rats with postweaning social isolation and ketamine treatment (NaTr); 15th generation of selectively bred animals without any treatment (SelNo) or selectively bred rats with both isolation and ketamine treatment (SelTr). The startle reaction, tail-flick and novel object recognition tests were used to classify the animals into low- or high-risk for schizophrenia. Reduced pain sensitivity, higher degree of the startle reaction, disturbed prepulse inhibition, altered motor activity and decreased differentiation index in the memory test were observed in the 15th generation of the substrain, along with enhanced grooming behavior. Five functional indices (TF latency, startle reaction, prepulse inhibition, differentiation index, and grooming activity) were rated from 0 to 2, and the analysis of the summarized score revealed that the NaNo group had the lowest overall indication of schizophrenic-like signs, while the SelTr animals scored the highest, suggesting that both heritable and environmental factors were important in the generation of the behavioral alterations. We assume that further breeding after this complex treatment may lead to a valid and reliable animal model of schizophrenia.

Visual pathways serving motion detection in the mammalian brain.

Motion perception is the process through which one gathers information on the dynamic visual world, in terms of the speed and movement direction of its elements. Motion sensation takes place from the retinal light sensitive elements, through the visual thalamus, the primary and higher visual cortices. In the present review we aim to focus on the extrageniculo-extrastriate cortical and subcortical visual structures of the feline and macaque brain and discuss their functional role in visual motion perception. Special attention is paid to the ascending tectofugal system that may serve for detection of the visual environment during self-motion.

Antinociceptive interactions between anandamide and endomorphin-1 at the spinal level.

1. Although it is well known that the combined administration of synthetic or plant-originated opioids with cannabinoids (CB) results in synergistic antinociception, the effects of combined administration of endogenous ligands acting at micro-opioid and CB receptors are not known. The aim of the present study was to determine the interaction between anandamide (AEA; a CB(1) receptor agonist) and endomorphin-1 (EM-1; a micro-opioid receptor agonist) after intrathecal administration. 2. Nociception was assessed by the paw-withdrawal test after carrageenan-induced inflammation in male Wistar rats. 3. Endomorphin-1 (16.4 pmol to 16.4 nmol) and AEA (4.3-288 nmol) alone dose-dependently decreased carrageenan-induced thermal hyperalgesia, although the highest dose of AEA also exhibited pain-inducing potential. The potency of AEA was approximately 59-fold lower than that of EM-1 (35% effective dose (ED(35)) 194.4 vs 3.3 nmol, respectively). Coadministration of these ligands revealed that combinations of 16.4 pmol EM-1 plus 28.8 or 86.5 nmol AEA were more effective than either drug alone, but other combinations were no more effective than the administration of EM-1 itself. Therefore, coadministration of AEA did not significantly shift the dose-response curve to EM-1. 4. The results of the present study indicate that the coadministration of AEA and EM-1 results in potentiated antihyperalgesia only for a combination of specific doses. Because AEA activates other receptor types (e.g. TRPV1) in addition to CB(1) receptors, the results of the present suggest that, after the coadministration of EM-1 and AEA, complex interactions ensue that may lead to different outcomes compared with those seen following the injection of exogenous ligands.

[Neurophysiological background of pain in the orofacial area: review of the literature]. / Az orofaciális terület fájdalmainak neurofiziológiai háttere. Osszefoglaló referátum.

The article presents an overview on the peripheral and central neural mechanisms underlying pain in the orofacial area. First a definition of pain and a description of general aspects of orofacial pain are presented. Characteristics of acute and chronic pain are also described. The study highlights the sense organs, the molecular mechanisms and categories of primary afferents involved in peripheral events of orofacial pain. After describing the brain-stem nuclei participating in trigeminal pain and their functional role, primary afferents involved in nociceptive sensation from the tooth pulp, explanations of dentinal sensitivity and differences between the brain-stem endings of primary afferents among different species are discussed in details. The role of higher brain centres, with a special emphasis on the thalamus and somatosensory cortex in the development of orofacial pain sensation is considered. The last section provides a review about how the activities of nociceptive neurons are controlled by higher brain centres and neurochemicals involved in pain transmission.

Multisensory responses and receptive field properties of neurons in the substantia nigra and in the caudate nucleus.

The basal ganglia are widely regarded as structures involved in sensorimotor co-ordination, but little is known about the sensory background of their function. We publish here descriptions of the excitatory sensory responses and receptive field properties of the visual, auditory, somatosensory and multisensory caudate nucleus and substantia nigra pars reticulata neurons. Altogether 111 caudate nucleus and 124 substantia nigra sensory neurons were recorded in halothane-anaesthetized, immobilized, artificially ventilated cats. The sensory properties of the caudate and nigral neurons were found to be quite similar. A majority of the units were unimodal while a significant proportion of them were multisensory. The visual and the somatosensory modalities predominated for both nuclei. The sensory receptive fields were extremely large. The visual and auditory receptive fields covered the whole physically approachable sensory field and the somatosensory receptive fields covered the whole body surface of the animal. The receptive field properties of the multisensory caudate and nigral units were similar to those of the unimodal neurons. We observed no signs of retinotopical or somatotopical organization within the basal ganglia. The particular sensory receptive field properties, together with the significant number of multisensory neurons in the basal ganglia, suggest the existence of a multisensory pathway of presumably tectal origin involving the caudate nucleus and the substantia nigra that may serve for the sensory feedback of motor actions co-ordinated by the basal ganglia.

Distributed population coding of multisensory spatial information in the associative cortex.

This study describes a possible mechanism of coding of multisensory information in the anterior ectosylvian visual area of the feline cortex. Extracellular microelectrode recordings on 168 cells were carried out in the anterior ectosylvian sulcal region of halothane-anaesthetized, immobilized, artificially ventilated cats. Ninety-five neurons were found to respond to visual stimuli, 96 responded to auditory stimuli and 45 were bimodal, reacting to both visual and auditory modalities. A large proportion of the neurons exhibited significantly different responses to stimuli appearing in different regions of their huge receptive field. These neurons have the ability to provide information via their discharge rate on the site of the stimulus within their receptive field. This suggests that they may serve as panoramic localizers. The ability of the bimodal neurons to localize bimodal stimulus sources is better than any of the unimodal localizing functions. Further, the sites of maximal responsivity of the visual, auditory and bimodal neurons are distributed over the whole extent of the large receptive fields. Thus, a large population of such panoramic visual, auditory and multisensory neurons could accurately code the locations of the sensory stimuli. Our findings support the notion that there is a distributed population code of multisensory information in the feline associative cortex.

Light therapy increases visual contrast sensitivity in seasonal affective disorder.

The purpose of this study was to investigate the effects of light therapy on visual contrast sensitivity in patients with seasonal affective disorder (n=10) and healthy control subjects (n=10). Static and dynamic visual contrast sensitivity was measured using a Venus system before and after 4 weeks of light therapy (10,000 lux, 30 min, 5 times a week). Light therapy increased static visual contrast sensitivity in the patients. We found no significant difference between the patients and controls either before or after light therapy. These results raise the possibility that light therapy induces retinal sensitization in seasonal affective disorder.

Antinociceptive activity of Sempervivum tectorum L. extract in rats.

The extract of Sempervivum tectorum L. (Crassulaceae) containing several flavonoids is widely used as an antiinflammatory agent in folk medicine. Previous studies have demonstrated that various flavonoids or flavonoid-containing plant extracts produce significant antinociception, but no data are available concerning their antinociceptive effect especially at the spinal level. The purpose of the present study was to investigate the antinociceptive activity of Sempervivum tectorum L. extract on acute and inflammatory pain sensitivity in awake rats. The pain sensitivity was assessed by the acute tail- flick test in intact rats and by the paw withdrawal test after carrageenan-induced inflammation using heat stimulus. The plant extract was administered intraperitoneally and intrathecally in rats. The intraperitoneal injection of a high dose of the extract (1000 mg/kg) significantly (p < 0.05) increased the paw withdrawal latency of the inflamed paw. The intrathecal administration (30-300 micro g) caused a small, but significant increase (10%-15%) in tail- flick latency. In the carrageenan-induced inflammatory model, the intrathecally applied extract (30-1000 micro g) significantly decreased, but did not relieve the thermal hyperalgesia. The results suggest that the spinal cord does not seem to play an important role in the antinociceptive effects of this plant extract.