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Biomedical subjects

A Pert

Publications and source records attributed to A Pert.

At least 91 records · Page 5Linked to original sources

Metabolic mapping of the brain during rewarding self-stimulation.

Local rates of cerebral glucose utilization were measured in rats by the quantitative 2-deoxy-D-[14C]glucose autoradiographic method during electrical stimulation of the ventral tegmental area. Rats trained in intracranial self-stimulation showed a pattern of changes in forebrain metabolic activity distinctly different from the pattern seen in rats stimulated by the experimenter. These findings provide information about the distribution of local cerebral activity specific to reinforced instrumental behavior.

Animals↗

Effects of lithium on [3H](-)quinuclidinyl benzilate [( 3H](-)QNB) binding to rat brain muscarinic cholinergic receptors.

Addition of lithium in vitro inhibited the binding of [3H](-)QNB to muscarinic cholinergic receptors of homogenates of tissue prepared from the striatum, cortex, and hippocampus of rat brain. Chronic in vivo exposure of rats to lithium in their food produced serum levels of lithium comparable to therapeutic levels. After in vivo exposure, the tissue homogenates prepared from these rats had an apparent decrease in receptor density in the three brain areas. However, if the tissue homogenates were washed twice, before addition to the assays, no differences in binding were detectable. Similar effects on unwashed and washed tissue homogenates can be demonstrated after in vivo exposure to lithium. Therefore, the apparent decrease in binding after in vivo lithium treatment is probably due to lithium retained in the tissue. No permanent alterations in the muscarinic receptor characteristics were measurable after the removal of the lithium. Nevertheless, in vivo interactions at muscarinic receptors may be important under conditions when therapeutic levels of lithium are present.

Animals↗

Chronic morphine-induced hyperactivity in rats is altered by nucleus accumbens and ventral tegmental lesions.

Lesions of the nucleus accumbens (NA) and the ventral tegmental area (VTA) attenuated and delayed the onset of the locomotor excitatory effects of morphine following chronic administration. Neither lesion, however, totally prevented the increase in locomotor excitation. These findings suggest that while the NA and VTA seem to play a role in mediating the excitatory effects of morphine, other regions and brain circuits must also be involved.

Animals↗

Endocrine effects of the cold pressor test: relationships to subjective pain appraisal and coping.

Blood was drawn from 14 normal volunteers twice before, immediately after a 1-minute immersion of the nondominant hand in ice water (cold pressor test), and twice during recovery. Serum levels of beta-endorphin, cortisol, prolactin, growth hormone, and opioid activity were determined, and measures of subjective pain appraisal and coping styles were obtained. Cortisol was the only variable to show a significant increase as a function of noxious stimulation. Correlational analysis yielded relationships between neuroendocrine variables and subjective pain appraisal as well as coping styles, suggesting complex interactions between neuroendocrine and psychological processes in human pain.

Adult↗

Changes in local cerebral glucose utilization during rewarding brain stimulation.

The quantitative 2-deoxy[14C]glucose method was used to determine local cerebral glucose utilization in unrestrained rats responding (lever-press) for rewarding electrical stimulation to area A10 (ventral tegmental area) and in similarly implanted inactive controls. Self-stimulation was associated with significant increases in metabolic activity, highly circumscribed in the ventral tegmental area, that continued rostrally within a rather compact zone of activity through the medial forebrain bundle, extending via the diagonal band of Broca to the level of the preoptic area. In the forebrain terminal areas bilateral increases in local cerebral glucose utilization were noted in the nucleus accumbens, lateral septum, hippocampus, and the mediodorsal nucleus of the thalamus. Ipsilateral (i.e., side of stimulation) increases in glucose utilization were noted in the bed nucleus of the stria terminalis, the basolateral and central amygdaloid nuclei, and the medial prefrontal cortex. Caudal to the stimulation site, increases in glucose utilization were found in the midline dorsal raphe, the ipsilateral pontine gray, medial parabrachial nucleus, and the locus coeruleus. Significant bilateral increases were noted in various sensory and motor areas. These results indicate that rather than a diffuse pattern of activity, rewarding brain stimulation is associated with discrete activation of specific neuronal projection fibers and selective terminal sites.

Animals↗

Differential effects of carbamazepine and lithium on sensitization and kindling.

Lithium carbonate appears to inhibit the development of cocaine-induced behavioral sensitization while it does not inhibit the development of amygdala kindling. Lithium chloride did not inhibit kindled seizures. Carbamazepine does not inhibit cocaine-induced motor activity or the development of behavioral sensitization in the rat. Carbamazepine is highly effective in blocking completed amygdala-kindled seizures, but does not block their development in the rat. Lithium carbonate and carbamazepine, two drugs of use in the prophylactic treatment of affective illness, appear to have differential effects on sensitization and kindling.

Amygdala↗

Opiate receptor localization in rat cerebral cortex.

The differential distributions of [3H]naloxone-labeled and [3H]D-Ala-D-Leu-enkephalin-labeled opiate receptors in rat cerebral cortex were localized autoradiographically and quantified by grain counting and computerized densitometry. In addition, receptor distributions were compared to terminal patterns of thalamocortical projections labeled by axoplasmic transport of [3H]amino acids. Opiate receptors labeled with [3H]naloxone in a mu ligand selectivity pattern show striking laminar heterogeneity and are densest in limbic cortical areas, intermediate in the motor cortex, and fewest in the primary sensory areas. By contrast, opiate receptors labeled with [3H]D-Ala2-D-Leu5-enkephalin in a delta ligand selectivity pattern are much more homogeneously distributed across both regions and laminae within regions. Mu receptors in most cortical areas have density peaks in layers I and VI and each peak shows a density gradient that is sloped within the layer so that the highest densities are at the most superficial and the deepest portions of cortex. In addition, there is an intermediate peak whose laminar position varies depending on the area in which it is found. In rostral agranular cortex, including limbic and motor areas, the [3H]naloxone binding peaks are in layers I, III, and VI. In primary somatosensory cortex, the intermediate peak is in layer Va and in most of remaining homotypical cortex it is in layer IV. Some areas have only bilaminar labeling, in superficial and deep layers; these include portions of the sulcal and retrosplenial cortices. Piriform and entorhinal cortices have dense [3H]naloxone binding only in the deepest layer and show a descending gradient of density toward the superficial layer. The positions of the mu receptor peaks were compared with termination patterns of projections originating in the thalamus. Close correspondence was found between receptor binding in the prelimbic, primary somatosensory, and entorhinal areas and projection terminations arising from the thalamic mediodorsal, posterior, and central medial nuclei, respectively. Although regional variations in [3H]D-Ala2-D-Leu5-enkephalin-labeled receptor density are uncommon, a gradual decrease in the number of sites along the dorsomedial wall of the cortex from anterior cingulate to caudal retrosplenial limbic cortex can be observed. Laminar variations in binding density are small as well; higher concentrations of the peptide binding sites are usually found in the deep cortical layers. These findings emphasize aspects of opiate receptor architecture which may be relevant to identifying cortical "opiatergic" neurocircuitry and raise the possibility of opiate modulation of thalamocortical transmission.

Animals↗

Effect of lidocaine pretreatment on cocaine-induced behavior in normal and amygdala-lesioned rats.

Animals treated with daily lidocaine (60 mg/kg, i.p.) develop progressive increases in pathological eating of nonnutritive substances, i.e. omniphagia. Bilateral amygdala lesions blocked the development of lidocaine-induced omniphagia. Following 32 daily injections of lidocaine, both lesioned and nonlesioned animals showed greater cocaine-induced hyperactivity than saline-pretreated controls. These data suggest cross-sensitization between the two local anesthetics lidocaine and cocaine, even though lidocaine does not possess the psychomotor stimulant effects of cocaine. Amygdala-lesioned animals showed greater cocaine-induced vertical rearing activity compared to controls. The lesion data suggest that the amygdala is differentially involved in the progressive behavioral sensitization to both chronic lidocaine and cocaine.

Amygdala↗

Alterations in rat central nervous system endorphins following transauricular electroacupuncture.

Auricular electro-stimulation (electroacupuncture) was found to produce naloxone-reversible analgesia in the rat. These behavioral effects were accompanied by significant increases in cerebrospinal fluid (CSF) levels of endorphins with concomitant decreases in the basomedial hypothalamus and medial thalamus of beta-endorphin-like immunoreactivity as well as endorphin-like radioreceptor activity. In addition, the radioreceptor assay also revealed a decrease in endorphin-like radioreceptor activity in the periaqueductal gray (PAG) matter. These results are interpreted to imply that electroacupuncture in the rat produces at least part of its analgesic action by activating central nervous system endorphinergic circuitry which results in a release and depletion of endorphins in certain brain loci and a concomitant elevation in the CSF. Hypophyseal endorphins do not appear to be involved in mediating acupuncture-induced analgesia in the rat since plasma levels of endorphins were not altered by this manipulation.

Acupuncture Therapy↗

Opiate receptor gradients in monkey cerebral cortex: correspondence with sensory processing hierarchies.

In order to obtain information on the possible functions of endogenous opiates in the primate cerebral cortex, we assessed the distribution of mu-like opiate receptors (which selectively bind 3H-labeled naloxone) and delta-like opiate receptors (which selectively bind 3H-labeled D-Ala2, D-Leu5-enkephalin) throughout the cerebral cortex of the rhesus monkey. Stereospecific [3H]naloxone binding sites increased in a gradient along hierarchically organized cortical systems that sequentially process modality-specific sensory information of a progressively more complex nature. Specific [3H]enkephalin binding sites, in contrast, were relatively evenly distributed throughout the cerebral cortex. These results, in combination with electrophysiological studies of monkeys and humans, suggest that mu-like opiate receptors may play a role in the affective filtering of sensory stimuli at the cortical level, that is, in emotion-induced selective attention.

Animals↗

The effect of amygdala kindling on spontaneous and cocaine-induced motor activity and lidocaine seizures.

Interactions of amygdala kindling and drug effects were explored in two experiments. Pretreatment with cocaine (40 mg/kg, IP) for 10 days did not significantly affect the rate of amygdala kindling compared to saline or non-kindled controls. In contrast, daily amygdala kindling with 200 microA for 0.5 s for 20 days substantially altered subsequent behavioral responses in a long-lasting fashion. Animals showed decreased spontaneous vertical rearing activity, as well as decreased cocaine-induced vertical activity. In contrast, they were more reactive to the direct dopamine receptor agonist apomorphine. Eighteen days following completion of amygdala kindling, kindled animals were more sensitive to lidocaine-induced convulsions; 88% of kindled animals, but only 24% of the implanted sham-stimulated controls, had seizures. These data suggest that amygdala kindling may produce long-lasting changes in selected spontaneous and drug-induced behaviors, as well as convulsive thresholds. Possible physiological and neurological changes underlying this altered responsivity are discussed.

Amygdala↗

Assessing pharmacologically induced dopamine receptor sensitivity changes with the Ungerstedt turning model.

Rats were lesioned unilaterally in the substantia nigra with 6-hydroxydopamine. Turning in response to apomorphine and amphetamine was assessed before and 5 days after 3-week treatment with haloperidol. After haloperidol withdrawal, contralateral turning, measured at 5 min following IP injection of 1 mg/kg apomorphine, was significantly less than before haloperidol treatment and ipsilateral turning, measured at 30 min following IP injection of 2 mg/kg amphetamine, was significantly greater than before the haloperidol treatment. These results suggest that dopamine receptor sensitivity increased on the unlesioned side compared to the lesioned side.

Amphetamine↗

Release of alpha-melanocyte stimulating hormone into rat and human cerebrospinal fluid in vivo and from rat hypothalamus slices in vitro.

The release of alpha-melanocyte stimulating hormone (alpha-MSH) from central nervous system neurons was investigated and demonstrated in vivo and in vitro. alpha-MSH immunoreactivity in rat and human cerebrospinal fluid (CSF) is comprised of deacetylated alpha-MSH, alpha-MSH and the methionine sulfoxide forms of these peptides. The sulfoxides are formed artifactually upon extraction. alpha-MSH in rat CSF is unaffected by hypophysectomy but is markedly increased by electrical stimulation of the mesencephalic central gray. These data indicate that CSF alpha-MSH is primarily of neuronal origin, alpha-MSH is also released in a calcium dependent manner from hypothalamic slices in vitro. The fact that the release of alpha-MSH is stimulated by veratridine and inhibited by tetrodotoxin demonstrates the necessity for neuronal sodium influx for alpha-MSH release. The presence of an alpha-MSH neurosecretory process supports a neurotropic role for this peptide in the central nervous system.

Animals↗

Bombesin: receptor distribution in brain and effects on nociception and locomotor activity.

The radioreceptor assay was used to examine the distribution of bombesin receptors in the rat brain. The highest concentrations of receptors appeared to be associated with limbic forebrain and midbrain structures such as the hippocampus, amygdala, hypothalamus and the periaqueductal gray matter. The caudate-putamen of the extrapyramidal motor system and the forebrain also exhibited high bombesin binding. Intraventricular injections of bombesin (0.1, 1.0 and 10 microgram) produced a dose-dependent increase in locomotor activity in rats. Injections of bombesin into the periaqueductal gray matter produced an antinociceptive reaction in the hot-plate as well as the tail-flick test. This apparent analgesia was not antagonized by naloxone.

Animals↗