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Pharmacological characterization of neuropeptide Y-(2-36) binding to neuropeptide Y Y1 and Y2 receptors.

Neuropeptide Y-(2-36) has been reported by several research groups to be a more potent orexigenic agent than intact neuropeptide Y. Therefore, it has been proposed that a novel 'Y1 variant' may modulate ingestive behavior. To define the receptor subtype involved in neuropeptide Y-stimulated feeding behavior, we evaluated the binding properties of neuropeptide Y-(2-36) and [125I]neuropeptide Y-(2-36) in established neuropeptide Y1 and Y2 containing cell lines and tissues. Neuropeptide Y-(2-36) displaced [125I]peptide YY binding to SK-N-MC cells (neuropeptide Y Y1 receptors) with a Ki of 3.69 nmol and SK-N-BE(2) cells (neuropeptide Y Y2 receptors) with a Ki of 3.08 nmol. Neuropeptide Y-(2-36) also displaced [125I]peptide YY binding to rat cerebral cortex, hippocampus and olfactory bulb with similar affinities. To examine the brain distribution of [125I]peptide YY, [125I]neuropeptide Y and [125I]neuropeptide Y-(2-36), adjacent sections were labeled and the binding sites detected by autoradiography. A similar distribution of binding was observed for each radioligand in all regions examined. Therefore, neuropeptide Y-(2-36) binds non-selectively to neuropeptide Y Y1 and neuropeptide Y Y2 receptors, but with lower affinity than neuropeptide Y and peptide YY. The increased potency and selectivity seen with neuropeptide Y-(2-36) in feeding studies cannot be explained on the basis of a unique in vitro pharmacology.

Animals↗

Autoradiographic analysis of 5-HT2A binding sites in the brain of Sardinian alcohol-preferring and nonpreferring rats.

The density of 5-HT2A binding sites in the brain of Sardinian alcohol-preferring (sP) and nonpreferring (sNP) rats was evaluated, using [3H]ketanserin for quantitative autoradiography. The highest [3H]ketanserin binding levels were found in the anterior olfactory nucleus, prefrontal cortex, medial prefrontal cortex, post-genual anterior cingulate cortex, insular cortex and claustrum. Statistically significant differences between sP and sNP rats were found in prefrontal cortex, medial prefrontal cortex and post-genual anterior cingulate cortex, where sP rats showed about 20% lower [3H]ketanserin binding levels. No significant difference was found in other areas, although some of them showed slightly lower [3H]ketanserin binding density in sP rats. The 5-HT2A receptor agonist, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane hydrochloride (DOI), microinjected into the medial prefrontal cortex, induced a lower number of wet dog shakes in sP than in sNP rats. These results indicate a different density of 5-HT2A binding sites, and a different functional regulation of 5-HT2A receptor mechanisms in discrete brain areas of sP, in comparison to sNP rats. These findings, and those showing lower levels of 5-HT in the frontal cortex of sP rats, suggest that altered 5-HT function in fronto-cortical areas could be linked to the genetic predisposition to high voluntary ethanol intake in these rats.

Alcohol Drinking↗

Vasoactive intestinal peptide in the brain of a mouse model for Down syndrome.

The most common genetic cause of mental retardation is Down syndrome, trisomy of chromosome 21, which is accompanied by small stature, developmental delays, and mental retardation. In the Ts65Dn segmental trisomy mouse model of Down syndrome, the section of mouse chromosome 16 most homologous to human chromosome 21 is trisomic. This model exhibits aspects of Down syndrome including growth restriction, delay in achieving developmental milestones, and cognitive dysfunction. Recent data link vasoactive intestinal peptide malfunction with developmental delays and cognitive deficits. Blockage of vasoactive intestinal peptide during rodent development results in growth and developmental delays, neuronal dystrophy, and, in adults, cognitive dysfunction. Also, vasoactive intestinal peptide is elevated in the blood of newborn children with autism and Down syndrome. In the current experiments, vasoactive intestinal peptide binding sites were significantly increased in several brain areas of the segmental trisomy mouse, including the olfactory bulb, hippocampus, cortex, caudate/putamen, and cerebellum, compared with wild-type littermates. In situ hybridization for VIP mRNA revealed significantly more dense vasoactive intestinal peptide mRNA in the hippocampus, cortex, raphe nuclei, and vestibular nuclei in the segmental trisomy mouse compared with wild-type littermates. In the segmental trisomy mouse cortex and hippocampus, over three times as many vasoactive intestinal peptide-immunopositive cells were visible than in wild-type mouse cortex. These abnormalities in vasoactive intestinal peptide parameters in the segmental trisomy model of Down syndrome suggest that vasoactive intestinal peptide may have a role in the neuropathology of Down-like cognitive dysfunction.

Animals↗

Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia?

Localization of the mRNAs for fractalkine, a CX3C chemokine, and for its receptor CX3CR1 was investigated in the rat brain. In situ hybridization study revealed that fractalkine mRNA was dominantly expressed in neuronal cells particularly in the olfactory bulb, cerebral cortex, hippocampus, caudate putamen and nucleus accumbens. In vitro study using enriched neuronal or glial culture supported the dominant expression of fractalkine mRNA in neurons. On the other hand, CX3CR1 mRNA was dominantly expressed in glial cells throughout the whole brain. The in vitro study suggested the cells expressing CX3CR1 mRNA are microglia, not astrocytes or neurons. Fractalkine appears to function as a signal molecule from neuron to microglia.

Amino Acid Sequence↗

Laminar redistribution of a glial subtype in the chick optic tectum.

Lamination is a central feature of structural organization and segregation within the central nervous system. Afferent fibers typically restrict their synapses to only one or a few specific laminae in the target region. Astroglial cells act as boundary markers for functional segregation of inputs in somatosensory cortex and the olfactory bulb and might also help to segregate particular connections in the neostriatum. This work presents evidence that a subset of astroglial cells expressing the carbohydrate recognized by tomato lectin are enriched in retino-non-recipient laminae of the chick optic tectum. This segregation is dependent upon retinal innervation; enucleated chick tecta contain cells that bind tomato lectin but do not segregate into their normal laminae. These results suggest that tomato lectin positive astrocytes of the superficial chick tectum play a role in defining or restricting lamina specific connections of retinal axons.

Animals↗

Expression of serotonin transporter protein in developing rat brain.

Serotonin transporter (5-HTT), a transmembrane protein, has been shown in adult brain to be distributed not only on synaptic terminals but to a great extent on axons as well. Here we report the ontogeny of 5-HTT and its relationship with serotonin (5-HT) neurons using established 5-HTT and 5-HT antibodies. Both 5-HTT- and 5-HT-immunostaining (-im) appear in 5-HT neurons at embryonic day 12 (E12) in rostral raphe nuclei (RRN). Soon after appearing, 5-HTT-im is highly expressed on axons, similar to adult expression. However, in contrast to adult, 5-HTT-im also outlines the soma-dendrites. Rich 5-HTT-im appears along the entire length of projecting axons, extending to the growth tip. In the next 2 days, intensive 5-HTT-im axons from RRN travel a course preferentially in the floor plate and later, the medial forebrain bundle trajectory. A group of new 5-HT-im neurons and 5-HTT-im axons appear at E13 in caudal raphe nuclei. At E16-18, taking the exact trajectory course of 5-HT axons, 5-HTT-im axons reach ganglionic eminence, olfactory bulb, and cortex and disperse into many brain regions in E18-20. No 5-HTT-im cell bodies were seen in nigral, locus ceruleus, or hypothalamus. However, the transient expression of 5-HTT on non-serotonergic system was seen in cortical and striatal neuroepithelia at E12 and sensory thalamic pathways at P0-P10. Prominent 5-HTT-im fibers in thalamocortical bundles project from sensory thalamic nuclei through reticular nucleus, internal capsule bundle and form barrels in somatosensory cortices. No 5-HTT-im was seen in glia-like cells using currently available antibody. These observations indicate that 5-HTT is: (a) associated preferentially with 5-HT neurons in brainstem, (b) temporally co-expressed with 5-HT in 5-HT neurons, (c) expressed on axons prior to synaptical sites at target neurons, which strongly indicates a volumic (extrasynaptic) transmission, (d) expressed in non-5-HT neurons within a specific window, which may affect the development of the systems "borrowing" the 5-HT. The early appearance of 5-HTT may also endow functionality as well as vulnerabilities of 5-HT, sensory thalamic, and cortical neurons to 5-HTT targeting drugs during pregnancy and after birth.

Animals↗

c-fos mRNA expression associated with PGF(2alpha)-induced nest-building behaviour in female pigs.

Domestic pigs, Sus scrofa, build a maternal nest on the day before parturition. A model for nest building has been established in pigs, in which exogenously administered prostaglandin (PG) F(2alpha) may be used to elicit nesting behaviour in cyclic, pseudopregnant and pregnant pigs. The central mechanisms mediating this response are unknown. The present study determined regional brain activity using semi-quantitative analysis of c-fos mRNA, after induction of nest-building behaviour by PGF(2alpha) in Large White pseudopregnant pigs. Oestradiol valerate injections (5 mg/day) were given on days 11-15 of the oestrous cycle to induce pseudopregnancy. The pigs were housed individually in pens (2.8 x 1.7 m) containing straw. On the test day (day 46 or 47 of pseudopregnancy) animals were injected with 3 ml saline (n=5) or 15 mg of PGF(2alpha) (Lutalyse, Upjohn; n=6) intramuscularly. Pigs treated with PGF(2alpha), but not saline, displayed bouts of rooting, pawing and gathering straw, which we interpret as nest building behaviour. The pigs were killed 65 min after treatment, which was 30 min after peak nest building activity, and the brain, uterus and ovaries removed for processing using in situ hybridisation. Saline-treated pigs had elevated levels of c-fos mRNA, compared to background, in the pituitary, corpus luteum and uterus, and a lower, but elevated, level of expression in cerebellum, cortex, hippocampus and olfactory bulb. PGF(2alpha)-treated pigs had significantly higher levels of c-fos mRNA expression than saline-treated pigs in the parvocellular and magnocellular regions of the hypothalamic paraventricular nucleus, the supraoptic nucleus (including the pars dorso-medialis), the neural lobe of the pituitary gland and the cerebellum. PGF(2alpha)-treated pigs also had significantly higher c-fos induction in corpus luteum. These data show that the pattern of c-fos mRNA expression in specific brain areas is different between pigs that show PGF(2alpha)-induced nest building and saline-injected controls.

Animals↗

Differential expression and function of apoptosis-associated tyrosine kinase (AATYK) in the developing mouse brain.

Apoptosis-associated tyrosine kinase (AATYK) is a non-receptor type tyrosine kinase that is predominantly expressed in adult mouse brain. Although it is also expressed in developing brains, its expression pattern and physiological functions are unclear. In the present study, we analyzed expression profiles of AATYK in developing mouse brains and its functional role and subcellular localization in cultured cerebellar granule cells. Expression of AATYK mRNA and protein increased during postnatal brain development. Immunohistochemical analysis indicated that the protein was differentially expressed in postmitotic neurons within various brain areas including the olfactory bulb, cerebral cortex, hippocampus, thalamus, colliculus, cerebellum, and brain stem. Developmental increases in its expression were also observed in cultured cerebellar granule cells. AATYK protein was largely fractionated into the microsomal fraction and was immunocytochemically distributed in an ER-like meshwork of the granule cell soma, suggesting a possible association with the ER membrane. AATYK protein was also present in neurites. In immature granule cells, overexpression of wild-type AATYK promoted neurite outgrowth, whereas that of tyrosine kinase-defective mutant significantly inhibited it. These results suggest that, in addition to its role in cell death in mature neurons, AATYK has a unique role in promoting neurite extension through its tyrosine kinase activity in developing neurons.

Animals↗

Molecular cloning of mouse Doc2alpha and distribution of its mRNA in adult mouse brain.

We have previously isolated from a human brain cDNA library, a new protein having two C2-like domains which interact with Ca2+ and phospholipid, and named Doc2alpha. Doc2alpha is abundantly expressed in brain, where it is highly concentrated on the synaptic vesicle fraction, and is implicated in Ca2(+)-dependent exocytosis. We have isolated here a mouse Doc2alpha cDNA and determined the localization of its mRNA in adult mouse brain. The amino acid sequence of the mouse Doc2alpha cDNA is 92% identical with that of the human counterpart. Northern blot analysis and in situ hybridization on adult mouse brain sections have revealed that Doc2alpha is predominantly expressed in mouse brain, where it is expressed in neuronal cells, but not in non-neuronal cells. Doc2alpha is highly expressed in the olfactory bulb, cerebral cortex, hippocampus, amygdaloid complex, and ventromedial hypothalamus nucleus, but not in the cerebellum, caudate-putamen, or ventral thalamus. These results indicate that Doc2alpha is expressed heterogeneously in mouse brain, where it is predominantly expressed in neuronal cells, and suggest that Doc2alpha plays a specific role in the area where it is expressed.

Amino Acid Sequence↗

Molecular cloning and characterization of a novel developmentally regulated gene, Bdm1, showing predominant expression in postnatal rat brain.

Postnatal development, such as synapse refinement, is necessary for the establishment of a mature and functional central nervous system (CNS). Using differential display analysis, we identified a novel gene, termed Bdm1, that is more abundantly expressed in the adult brain than in the embryonic brain. The full-length Bdm1 cDNA is 2718 base pairs long and contains an open reading frame of 1059 base pairs encoding a 38-kDa protein. Northern blot analysis revealed that expression of Bdm1 mRNA in the brain was weak on embryonic days and increased in the early postnatal period. Bdm1 mRNA was significantly expressed in the brain and heart, but there was no or little expression in other tissues. During the differentiation of mouse carcinoma cells P19 to neuron-like cells by retinoic acid, Bdm1 mRNA was up-regulated almost parallel to neurofilament mRNA. Expression of Bdm1 mRNA was observed appreciably in PC12 cells after neuronal differentiation but not in the nonneural cell lines examined. In situ hybridization demonstrated that Bdm1 was expressed widely in the olfactory bulb, cerebral cortex, hippocampus, cerebellum, thalamus, and medulla oblongata. Taken together, these data suggest that Bdm1 gene plays a role in the early postnatal development and function of neuronal cells.

Amino Acid Sequence↗

Counteraction of spaceflight-induced changes in the rat central serotonergic system by adrenalectomy and corticosteroid replacement.

The effects of a 17-day spaceflight duration on serotonergic measures in various parts of rat brain have been studied (flight-SHAM group). The contribution of the activation of the hypothalamo-pituitary-adrenal axis (HPA) related to the response of the central serotonin system was evaluated in adrenalectomized with chronic corticosterone replacement rats (flight-ADX+CORT group). These two groups of rats were compared to their respective ground-based controls. Physiological parameters (body, adrenal and thymus weights) and corticosterone levels were measured. In flight-SHAM group as compared to controls, adrenal hypertrophy and elevation in plasma corticosterone levels (174%) were observed, without change in thymus mass. In most brain areas studied, significant decreases in TRP, 5-HTP and 5-HIAA were found associated with lower levels of 5-HT in cortex, thalamus and striatum. Conversely, there were elevations in TRP, 5-HTP levels in striatum and increases in 5-HIAA/5-HT ratios, an index of 5-HT turnover, in cortex, striatum and olfactory bulb while the hypothalamus was the sole region where a fall was observed. In ADX rats with chronic corticosterone replacement these effects were not observed in the majority of brain areas. It is concluded that a 17-day spaceflight exerted an inhibitory effect on serotonin metabolism, probably by activation of the HPA axis. The results could not distinguish between the effects of microgravity and the stress associated with landing.

Adrenal Glands↗

Biochemical and ultrastructural analyses of IgLON cell adhesion molecules, Kilon and OBCAM in the rat brain.

Kilon (kindred of IgLON) and opioid-binding cell adhesion molecule belong to the IgLON subgroup of immunoglobulin superfamily together with the limbic system-associated membrane protein and neurotrimin. In the present study, we have analyzed biochemical and ultrastructural characterization of Kilon and opioid-binding cell adhesion molecule such as regional and developmental expression patterns, light and electron microscopic localization, and intermolecular interactions. Western blotting revealed a widespread distribution pattern of Kilon with high expression levels in the olfactory bulb, cerebral cortex, diencephalon, hippocampus, and cerebellum and low expression levels in the medulla oblongata and spinal cord. In contrast, opioid-binding cell adhesion molecule showed a regionally restricted expression pattern with high levels only in the cerebral cortex and hippocampus. Expression of Kilon and opioid-binding cell adhesion molecule was increased gradually during postnatal development and maintained until adulthood. Light microscopic immunohistochemistry demonstrated that the localization of opioid-binding cell adhesion molecule and Kilon coincided well with that of vesicle-associated membrane protein 2, a synaptic marker protein, in the cerebral cortex and hippocampus of adult brain. In the cerebellum, Kilon-immunoreactive puncta were observed to colocalize well with that of vesicle-associated membrane protein 2, while opioid-binding cell adhesion molecule immunoreactivity was observed only at part of synaptic glomeruli in the granular layer and rare in the molecular layer. Electron microscopic analysis revealed that Kilon and opioid-binding cell adhesion molecule immunoreactivity was observed mainly at postsynaptic sites of dendritic and somatic synapses in adult cerebral cortex and hippocampus. Only trace levels of Kilon and opioid-binding cell adhesion molecule were detected in the soluble fraction of a cortical homogenate, although a substantial amount of F3 was present in the soluble fraction. A binding analysis using a cross-linker and the immunoprecipitation technique demonstrated that Kilon and opioid-binding cell adhesion molecule interacted heterophilically and homophilically. These findings show that Kilon and opioid-binding cell adhesion molecule are clearly distinguishable from each other in regional expression and localization, and binding patterns. These differences possibly represent diverse functions of each IgLON molecule.

Animals↗

Immunohistochemical localization of the somatostatin sst2(b) receptor splice variant in the rat central nervous system.

Somatostatin is a neuromodulator in the mammalian CNS. To date, genes for at least five different somatotrophin release inhibiting factor receptors, termed sst1-sst5, have been cloned. The rat sst2 receptor exists in two splice variants, sst(alpha)a) and sst2(b), which differ in their carboxy-termini. When heterologously expressed in Chinese hamster ovary-K1 cells, these splice variants show little difference in their operational characteristics. Recently, the distribution of the sst2(a) receptor was documented, yet at present no data are available about the distribution of the sst2(b) receptor in the CNS. Here, we present the characterization of a novel polyclonal anti-peptide antibody that is selective for the sst2(b) receptor splice variant. The antibody was raised against the unique intracellular carboxy-terminal portion of the receptor protein. Using this affinity-purified antibody in western blotting experiments, the sst2(b) receptor expressed in Chinese hamster ovary-K1 cells was shown to be a glycoprotein with a molecular weight centred at about 85,000. The antibody showed no cross-reactivity to any of the recombinant human sst1-5 receptors, the rat sst2(a) receptor or wild-type Chinese hamster ovary-K1 cells. Employing immunohistochemistry, we investigated the distribution of the sst2(b) receptor in the brain and spinal cord of adult rats. A distinct distribution was found throughout the rostrocaudal axis of the CNS. Somatodendritic as well as axonal staining was observed. Somatodendritic labelling was particularly obvious in the olfactory bulb, cerebral cortex, hippocampal formation, mesencephalic trigeminal nucleus and cerebellum, as well as in cranial and spinal motor areas. The results show that the distribution of the sst2(b) receptor partially overlaps with that of the sst2(b) receptor, although there were differences in a number of brain areas. The location of the sst2(b) receptor implies that it may mediate a modulatory role of somatostatin inhibitory releasing factor on sensory as well as motor functions.

Animals↗

Localization of cytosolic phospholipase A2 messenger RNA mainly in neurons in the rat brain.

Ca2(+)-sensitive 85,000 mol. wt cytosolic phospholipase A2 plays an essential role in the selective and stimulus-dependent release of arachidonic acid from membrane phospholipids. Cytosolic phospholipase A2-catalysed lipid mediators including arachidonic acid and its metabolites have been suggested to be involved in a variety of neuronal functions in the CNS. Since the cellular localization of cytosolic phospholipase A2 is still controversial and obscure, we tried an improved method of rapid processing of each specimens and succeeded in obtaining intense signals of cytosolic phospholipase A2 messenger RNA in the normal rat brain by northern blot analysis and in situ hybridization. Northern blot analysis showed the abundant distribution of cytosolic phospholipase A2 messenger RNA in most regions of the brain, with intense signals observed in the pineal gland and pons. Macroautoradiographs prepared after in situ hybridization with three different antisense riboprobes gave essentially similar patterns of localization; significant signals were widely detected in the gray matter of various regions, i.e. the olfactory bulb, cerebral cortex, hippocampus, amygdala, several thalamic and hypothalamic nuclei and cerebellum. Microautoradiographs showed that most of the intense signals were predominant in neurons, and that faint signals were from glial cells and other non-neuronal cells in the choroid plexus, inner surface cells of veins and the leptomeninges. In addition, the cycloheximide treatment increased the cytosolic phospholipase A2 messenger RNA level in the same cell populations originally possessing messenger RNA signals. Predominant expression of cytosolic phospholipase A2 messenger RNA in neurons may provide the basis for the contribution of cytosolic phospholipase A2-catalysed lipid mediators to a variety of neurotransmission and synaptic functions in the CNS.

Animals↗

High versus low reactivity to a novel environment: behavioural, pharmacological and neurochemical assessments.

Based on their rearing response to a novel open field, male Wistar rats were divided into two sub-groups with either high or low behavioural activity (high rearings, versus low rearings). These sub-groups were repeatedly exposed to the same open field and tested for behavioural habituation. Since we previously found neurochemical evidence for different cholinergic reactivities in such high rearing and low rearing rats, their behavioural responses to the muscarinic antagonist scopolamine (0.5 mg/kg) were also investigated in the open field. Additionally, they were exposed to the elevated plus-maze to test for possible differences in measures of anxiety. After behavioural testing, tissue concentrations of biogenic amines were determined in the ventral striatum (nucleus accumbens, olfactory tubercle), frontal cortex, striatum, hippocampus and amygdala. The results show that the higher rearing responses of high rearing rats in the novel open field were paralleled by higher locomotor activity. These behavioural differences between groups decreased with repeated open field exposure, an effect which was largely due to between-session habituation in high rearing rats. Thereby, high rearing rats approached the lower levels of low rearing rats, in which locomotor activity and rearings did not habituate between testing. Nevertheless, habituation was also observed in low rearing rats, especially in the measure of thigmotactic scanning, since the levels of scanning declined both between and within test sessions. The anticholinergic challenge with scopolamine induced a general pattern of behavioural activation. Furthermore, scopolamine partly reinstated the behavioural differences between high and low rearing rats that had been observed in the novel open field, since high rearing rats showed more rearing behaviour than low rearing rats under scopolamine. In contrast to the open field, there were no significant differences between high and low rearing rats in the plus-maze. The neurochemical analysis revealed, among others, higher dopamine levels in the ventral striatum of high rearing rats together with lower serotonin levels in the medial frontal cortex. The current findings thus indicate that high and low rearing rats not only differ in their behavioural response to a novel environment, but also in their patterns of behavioural habituation, and with respect to behaviour induced by an anti-cholinergic challenge. These differential behavioural profiles of high and low rearing animals are discussed with respect to the role of dopaminergic mechanisms in the forebrain, and the potential impact of cholinergic mechanisms.

Animals↗

Differential regional zif268 messenger RNA expression in an escalating dose/binge model of amphetamine-induced psychosis.

Amphetamine-induced psychosis is most often associated with a high-dose multiple binge pattern of stimulant abuse. To simulate these conditions in rats, we used an escalating dose/binge administration paradigm. Animals were pretreated with escalating doses of amphetamine (1.0-8.0mg/kg) over four days, then exposed to nine daily binges (8.0mg/kg every 2h; four injections/day). Other animals received either multiple injections of saline, saline followed by acute amphetamine (8.0mg/kg) or single daily injections of amphetamine (8.0mg/kg) in parallel with the escalating dose/binge treatment. One hour after the last injection, all animals were decapitated and regional brain activation patterns were assessed using in situ hybridization with antisense probes for zif268. Acute amphetamine resulted in a significant elevation of zif268 messenger RNA in both the nucleus accumbens and dorsal striatum. However, whereas after single daily amphetamine treatment this index was no longer elevated above control levels in the dorsal striatum, multiple binge exposures were required for the nucleus accumbens to return to baseline. Agranular insular cortex and medial olfactory tubercle zif268 messenger RNA expression was also markedly increased after acute amphetamine treatment but, unlike the nucleus accumbens and dorsal striatum, this increase was not significantly attenuated by either single daily injection or multiple binge treatment. Zif268 messenger RNA expression in the lateral nucleus of the amygdala also remained elevated above baseline after binge treatment. The possible relationships of these changes in zif268 messenger RNA regional expression patterns to the development of psychosis in high-dose stimulant abusers are discussed.

Amphetamines↗

Progesterone receptor isoforms expression in the prepuberal and adult male rat brain.

Progesterone receptor (PR) isoforms expression was determined in several regions of the prepuberal and adult male rat brain by using reverse transcription coupled to polymerase chain reaction. Rats under a 14:10-h light-dark cycle, with lights on at 0600 h were used. We found that in the hypothalamus of prepuberal animals the expression of both PR isoforms was similar, whereas PR-A expression was higher than that of PR-B in adults. In the cerebellum PR-B expression was predominant in both prepuberal and adult rats. In both ages PR-A and PR-B exhibited a non-significant tendency to be predominant in the hippocampus and the preoptic area respectively. In the frontal cortex and the olfactory bulb PR isoforms were expressed at a similar level. These results indicate a differential expression pattern of PR isoforms in the male rat brain and suggest that the tissue-specific expression of PR-A and PR-B is important for the appropriate response of each cerebral region to progesterone.

Age Factors↗

Episodic multiregional cortical coherence at multiple frequencies during visual task performance.

The way in which the brain integrates fragmentary neural events at multiple locations to produce unified perceptual experience and behaviour is called the binding problem. Binding has been proposed to involve correlated activity at different cortical sites during perceptuomotor behaviour, particularly by synchronization of narrow-band oscillations in the gamma-frequency range (30-80 Hz). In the rabbit olfactory system, inhalation induces increased gamma-correlation between sites in olfactory bulb and cortex. In the cat visual system, coherent visual stimuli increase gamma-correlation between sites in both the same and different visual cortical areas. In monkeys, some groups have found that gamma-oscillations transiently synchronize within striate cortex, superior temporal sulcus and somatosensorimotor cortex. Others have reported that visual stimuli produce increased broad-band power, but not gamma-oscillations, in several visual cortical areas. But the absence of narrow-band oscillations in itself does not disprove interregional synchronization, which may be a broad-band phenomenon. We now describe episodes of increased broad-band coherence among local field potentials from sensory, motor and higher-order cortical sites of macaque monkeys performing a visual discrimination task. Widely distributed sites become coherent without involving other intervening sites. Spatially selective multiregional cortical binding, in the form of broad-band synchronization, may thus play a role in primate perceptuomotor behaviour.

Animals↗