A unique tubulin antibody which disrupts particle movement in squid axoplasm.

Microtubules have been demonstrated to be a substrate for organelle transport and particle translocation in vitro and in vivo. Subsequent to a previous report of inhibition of axonal transport of exogenous tracers in vivo using antiserum NS-20 against tubulin (Johnston et al: Brain Res. 1986), we now show disruption of particle movement in extruded squid axoplasm using this unique immunological probe.

Brain development in the neonatally decorticated rat.

The brain weights, cross-sectional areas of subcortical structures, gross morphology, and retrograde degeneration in the thalamus and basal ganglia were compared in rats with neonatal (1 or 5 days of age) or adult ablation of all of the neocortex. Neonatal decorticate and control rats also were given injections of fluorescent retrograde tracers. True blue or Nuclear yellow into the striatum, hippocampus, or subiculum in order to identify afferent pathways to these structures.

Inhibition of axonal transport 'in vivo' by a tubulin-specific antibody.

We have used antibodies against the major proteins of the cytoskeleton-tubulin, the neurofilament triplet proteins and actin-as in vivo probes to determine the contribution of separate components of the cytoskeleton in axonal transport. The injection of either Fast Blue or wheat germ agglutinin conjugated horseradish peroxidase into the caudate nucleus of adult rats resulted in the retrograde transport of these tracers to the neuronal cell bodies in the substantia nigra pars compacta. In experimental animals these tracer injections were immediately preceded by injections of antiserum against tubulin, neurofilament triplet protein or actin, into multiple sites in the caudate.

Dopamine and opiate receptors: localization in the striatum and evidence for their axoplasmic transport in the nigrostriatal and striatonigral pathways.

The axoplasmic transport of dopamine and opiate receptors in the striatonigral and nigrostriatal pathways was investigated by placing coronal knife cuts through these pathways and examining autoradiographically the accumulation of receptors at the site of the cut. In otherwise normal animals build-up of both receptors was found both rostral and caudal to the cut after a survival time of 24 h. Build-up of both receptors was reduced caudal to the cut by prior 6-hydroxydopamine lesions of the substantia nigra-ventral tegmental area, and reduced rostral to the cut by prior kainic acid lesions of the striatum.

Pattern of intracranial and extracranial projections of trigeminal ganglion cells.

The trigeminal sensory innervation of the major cerebral vessels is thought to carry the nociceptive information during a migraine headache, and this pain is usually referred to the forehead area. Using retrograde tracing techniques, we have described the distribution of sensory trigeminal cells that innervate the middle cerebral artery (MCA) and the forehead. Nearest-neighbor analysis of the ophthalmic division of the trigeminal ganglion revealed that cells innervating the forehead tend to be clumped around individual cells that innervate the MCA.

Cell death organizes the postnatal development of the trigeminal innervation of the cerebral vasculature.

In the adult trigeminal ganglion single cell bodies that innervate the middle cerebral artery (MCA) are different from but situated near to one or more cell bodies that innervate the forehead (O'Connor and Van der Kooy, submitted). Multiple fluorescent retrograde axonal tracing in postnatal day 3-90 rats was employed to describe the development of this adult pattern of trigeminal projections. We found that close to 90% of the cells that innervate the MCA at postnatal day 5 (PND 5) are eliminated by PND 90.

The development of a patchy organization of the rat striatum.

The rat striatum can be divided into patch and matrix compartments. Patches, as marked by high opiate receptor binding, first emerge perinatally from a dense, diffuse field of striatal opiate binding. Our quantitative analysis revealed that the patch compartment formed its peak proportion of the total striatal area at postnatal day 7.

Visceral cortex lesions block conditioned taste aversions induced by morphine.

Rats with bilateral ibotenic acid or sham lesions of the visceral (agranular insular) cortex were tested for a conditioned taste aversion (CTA) to saccharin after five pairings of morphine sulphate injections (15 mg/kg IP) with consumption of a novel solution (0.1% saccharin). Lesioned animals demonstrated no evidence of the morphine-induced CTA that was seen in the sham operated animals.

Lesions of the area postrema and underlying solitary nucleus fail to attenuate the inhibition of feeding produced by systemic injections of cholecystokinin in Syrian hamsters.

A large body of evidence indicates that the intestinal hormone cholecystokinin (CCK) may serve as a signal for satiety. The abdominal vagus has been shown to be important for the satiety response to exogenous, and by inference, endogenous, CCK in rats and hamsters. Thus, it appears that stimulation of CCK receptors on afferent fibers of the abdominal vagus activates a gut-brain pathway to signal satiety.

Organization of the striatum: collateralization of its efferent axons.

The anatomical structure of the basal ganglia indicates that the input from the cerebral cortex is funnelled through the striatum to the globus pallidus and substantia nigra. This structure implies integration of the information as it is transferred through the basal ganglia. In order to investigate this integration, we studied the collateralization of striatal efferents to the globus pallidus and the substantia nigra-ventral tegmental area.

Hyperalgesia mediated by peripheral opiate receptors in the rat.

Behavioural experiments were undertaken to investigate the possible functional significance of opiate receptors located at peripheral endings of primary sensory neurons. The responses of animals to noxious chemical stimuli applied to the ear (ear scratch test) were measured after local pretreatment of these areas with etorphine. Local etorphine administration produced a low dose hyperalgesia and high dose analgesia.

Non-cholinergic globus pallidus cells that project to the cortex but not to the subthalamic nucleus in rat.

A substantial population of small globus pallidus neurons was demonstrated to have axonal projections to the cerebral cortex using fluorescent retrograde transport techniques. This population was separate from the more numerous population of medium size globus pallidus cells projecting to the subthalamic nucleus and was also separate from the pallidal and especially peripallidal population of large cholinergic cells projecting to the cortex. Some of the small, non-cholinergic cells projecting to the cortex also gave off axonal collaterals to the paraventricular thalamic nucleus.

Simultaneous ultrastructural localization of cholecystokinin- and tyrosine hydroxylase-like immunoreactivity in nerve fibers of the rat nucleus accumbens.

Ultrathin frozen sections were used to study the localization of cholecystokinin (CCK) in dopaminergic systems in the rat nucleus accumbens. Antibodies against CCK and tyrosine hydroxylase (TH), a synthetic enzyme of dopamine, were differentially visualized using protein A conjugated to colloidal gold particles of different sizes. Nerve processes were observed to be immunocytochemically labelled for either CCK or TH but also in some cases for both CCK and TH.

Opposite motivational effects of endogenous opioids in brain and periphery.

Many psychoactive drugs, including the opiates, have been shown to have paradoxical reinforcing effects. Opiates produce positive reinforcing effects when they are paired with visual and textural environmental stimuli in rats, yet, at similar doses and over the same routes of administration, produce aversive effects, as shown when they are paired with taste stimuli. Similarly, in human, the positive reinforcing effects of opiates are well known to addicts and recreational drug users, yet patients receiving opiates as analgesics often report nauseous reactions.

A serotonin-containing pathway from the area postrema to the parabrachial nucleus in the rat.

A combined retrograde tracing-immunofluorescent technique was used to identify the relationships between the cellular population projecting to the parabrachial nucleus and the serotonin-immunoreactive cell population of the area postrema in rats. The retrograde fluorescent tracer True Blue was injected in the parabrachial region and 3 days later the animals were perfused. Serial cryostat sections were processed for serotonin immunofluorescence.

Evidence on the retrograde neurotoxicity of doxorubicin.

Doxorubicin, a fluorescent retrograde neurotoxin, killed neurons in the ventral tegmentum and thalamus that were afferent to the injection site in the caudate-putamen. The neurotoxic effects in the ventral tegmentum and thalamus were prevented by a large coronal knife cut caudal to the injection site in the striatum, suggesting that retrograde transport of doxorubicin is necessary for the death of afferent neurons. In the striatum the neurotoxic effects of doxorubicin 14 days post-injection were quantitatively much greater on afferent neurons (as assessed by a 72% drop in dopamine levels) than on local striatal perikarya (as evidenced by the small 22% drop in the activity of glutamic acid decarboxylase).

Neuroleptics block the positive reinforcing effects of amphetamine but not of morphine as measured by place conditioning.

The role of dopamine brain systems in mediating the rewarding effects of opiates and stimulants was investigated using the conditioned place preference paradigm. The effects of the neuroleptics alpha-flupentixol (0.8 mg/kg, IP) and haloperidol (1.

Developmental relationships between opiate receptors and dopamine in the formation of caudate-putamen patches.

Opiate receptor distribution changes from a diffuse to a patchy pattern in the perinatal rat caudate-putamen. The opiate receptor patches are continuous with the patches of dopamine fluorescence seen in the perinatal striatum. Both types of patches match areas of relatively low neuronal cell density as seen in Nissl-stained sections.

The distribution and morphology of opioid peptide immunoreactive neurons in the cerebral cortex of rats.

Pharmacological and biochemical evidence has implied that a widespread opioid peptide system exists within the cerebral cortex to mediate a variety of opiate effects. However, immunocytochemical detection of opioid peptides in the cortex has been limited. Using antisera to enkephalin and bovine adrenal medullary peptide, both fragments of proenkephalin, and an antiserum to dynorphin A, a fragment of prodynorphin, we now describe the regional and laminar distribution of a widespread population of olfactory cortical and neocortical cell bodies and fibers with opioid immunoreactivity in rats.

The organization of projections from the cortex, amygdala, and hypothalamus to the nucleus of the solitary tract in rat.

Direct projections from the forebrain to the nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus in the rat medulla were mapped in detail using both retrograde axonal transport of the fluorescent tracer True Blue and anterograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). In the retrograde tracing studies, cell groups in the medial prefrontal cortex, lateral prefrontal cortex (primarily ventral and posterior agranular insular cortex), bed nucleus of the stria terminalis, central nucleus of the amygdala, paraventricular, arcuate, and posterolateral areas of the hypothalamus were shown to project to the NTS and in some cases also to the dorsal motor nucleus of the vagus. The prefrontal cortical areas projecting to the NTS apparently overlap to a large degree with those cortical areas receiving mediodorsal thalamic and dopaminergic input.

Area postrema: site where cholecystokinin acts to decrease food intake.

Administration of cholecystokinin (CCK) reduces food intake in rats. This effect of CCK was attenuated in rats with thermal lesions of the area postrema. This result was specific to CCK, as area postrema lesions had no effect on the reduction in food intake produced by amphetamine.

Behavioral effects of peripheral administration of arginine vasopressin: a review of our search for a mode of action and a hypothesis.

In this review we present data summarizing our studies concerning the mechanism of action for the behavioral effects of peripheral arginine vasopressin (AVP) administration. We have demonstrated a clear performance improvement in a one trial appetitive task designed to measure the memory-learning process. This behavioral effect is blocked by peptide analogs which block the pressor response to AVP.

Organization of the projections of a circumventricular organ: the area postrema in the rat.

The projections of the rat area postrema were analysed using anterograde and retrograde axonal transport techniques. Discrete injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the area postrema produced anterograde labeling in specific medullary and pontine nuclei. In the medulla, anterograde labeling was present in the internal solitary zone and dorsal division of the medial solitary nucleus, both of which also contained a small number of retrogradely labeled perikarya.

Motivational properties of ethanol in naive rats as studied by place conditioning.

The reinforcing properties of ethanol were examined in naive adult male rats by means of a place conditioning paradigm that has previously demonstrated the positive reinforcing properties of food, water and some drugs, and the aversive properties of punishers such as electric shock and lithium chloride. Only doses of 0.8-1.