Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Slices of olfactory cortex from guinea pig, incorporating the lateral olfactory tract (LOT), were maintained in a glucose-bicarbonate solution in vitro. Stimulation of the LOT produced: 1) A summed LOT action potential; 2) A monosynaptic surface-negative wave (N-wave); and 3) A polysynaptic surface-positive wave (P-wave) as recorded from the pial surface of the slice at 24 degrees C. During a period of single stimulus pulses to the LOT, local anesthetics and barbiturates, applied to the incubating solution, depressed the amplitude of the action potential (while increasing its latency and threshold) with the following potencies: tetracaine greater than cocaine greater than lidocaine greater than procaine greater than pentobarbital greater than phenobarbital. The order of potencies was similar for the synaptic potentials. Each local anesthetic or bartiturate first depressed the P-wave, the N-wave and then the LOT potential, with all three potentials being affected within a narrow range of drug concentrations. There was a good linear relationship between drug potency on all potentials and the distribution coefficients of the drugs in octanol-water. During a period of double stimulus pulses to the LOT, up to 10 seconds apart, low concentrations of barbiturates depressed the N-wave to the second pulse with little effect on the first, conditioning pulse, an effect not seen with local anesthetics. The bath concentrations required for this effect of both barbiturates were similar to previous reports of blood concentrations required for general anesthesia. It appears that local anesthetics have actions on brain similar to those reported for other tissues and that barbiturates share some of the actions of local anesthetics, but exert a selective depression on repetitively elicited synaptic potentials.
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PMID:Local anesthetics and barbiturates: effects on evoked potentials in isolated mammalian cortex. 119 35

The effect of molindone on the activity of dopaminergic (DA) neurons in the rat midbrain and on DA metabolism in the striatum and olfactory tubercles was studied using extracellular single unit recording and biochemical techniques respectively. Molindone in low intravenous doses (0.4-0.8 mg/kg) was found to reverse d-amphetamine and apomorphine induced depression of DA neurons and to block apomorphine induced depression of these cells. Molindone was also found to increase dopamine synthesis and dihydroxyphenylactic acid levels in the striatum and olfacotry tubercles. In all of these respects molindone behaves identically to most classical neuroleptics. However, unlike most antipsychotic drugs previously tested, molindone failed to increase the baseline firing rate of DA cells and blocked haloperidol induced increases in DA neuron activity. In this regard molindone most closely resembles thioridazine and clozapine. Possible mechanisms of action of molindone are discussed based on these findings.
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PMID:Effects of molindone on central dopaminergic neuronal activity and metabolism: similarity to other neuroleptics. 122 4

Depression of the electrically-evoked surface-negative field potential (N-Wave) by bath-superfusion of carbachol was measured in guinea-pig olfactory cortex slices maintained in vitro. The possibility that this response, previously proposed to be mediated via a presynaptic M1: muscarinic receptor, might in fact be due to M4 receptor activation, was investigated by testing the effectiveness of himbacine (a proposed M4-selective antagonist) on our cortical preparation. Himbacine (100 nM-1 microM) had no effect on the N-wave potential alone, but it induced a clear competitive-type inhibition of carbachol effects. Schild plot analysis (regression slope constrained to unity) of pooled data yielded a pA2 value of 7.2 for this antagonist (n = 7 slices). This value accords more with that expected for the interaction of himbacine with M1 receptors (approximately 7.2) than with functionally expressed M4 receptors (approximately 8.5-8.5). We therefore conclude that M4-type muscarinic receptors are unlikely to be involved in mediating this presynaptic carbachol response.
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PMID:Carbachol-evoked suppression of excitatory neurotransmission in guinea-pig olfactory cortex slices is unlikely to involve an M4-muscarinic receptor subtype. 131 58

Ablation of the olfactory bulbs in mice C57Bl/6j was accompanied by motor and orienting-exploratory activity augmentation in the "open field" test and deterioration of the learning ability to active and passive avoidance. The most expressed behavioural changes developed in four weeks after the surgery. Chronic administration of antidepressants (amitriptyline, 20 mg/kg; trazodone, 20 mg/kg; imipramine, 10 mg/kg; intraperitoneally) normalized behaviour of bulbectomized animals, trazodone being the most effective. In the biochemical studies the brainstem serotonin level was found to be decreased and the density of 5HT2-receptors in the cerebral cortex increased in bulbectomized mice. Only trazodone was able to correct the biochemical indices. The state of the bulbectomized mice is supposed to serve a model of a depression with hypo-function of serotonergic system of the brain.
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PMID:[The behavioral and biochemical sequelae of the removal of the olfactory bulbs in C57Bl/6j mice]. 133 99

Unilateral olfactory deprivation in the rat profoundly modifies olfactory bulb anatomy, chemistry and function. The present report examined the time-course of the functional effects of unilateral deprivation on inhibition in the olfactory bulb using paired-pulse stimulation of the lateral olfactory tract and olfactory nerve. In addition, an attempt was made to correlate these physiological measures with olfactory bulb dopamine and norepinephrine levels and tyrosine hydroxylase immunoreactivity. Deprivation from postnatal day 1 to postnatal day 20 or postnatal day 40 significantly enhanced lateral olfactory tract paired-pulse depression, while late onset deprivation (postnatal day 20) had no effect. Olfactory nerve paired-pulse depression was enhanced by 40 days of deprivation regardless of the age at onset. The time-course of these deprivation-induced physiological changes did not correlate well with reductions in dopamine. Dopamine levels were reduced in all deprivation conditions by 70-80% compared with control bulbs. Norepinephrine content was slightly elevated in deprived bulbs. These results suggest that early olfactory deprivation modifies olfactory bulb synaptic activity and further, as with other sensory systems, these effects are age and duration dependent.
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PMID:Functional consequences of unilateral olfactory deprivation: time-course and age sensitivity. 135 86

This paper reviews the clinical and experimental literature on patients with multiple adverse responses to chemicals (Multiple Chemical Sensitivity Syndrome-MCS) and develops a model for MCS based on olfactory-limbic system dysfunction that overlaps in part with Post's kindling model for affective disorders. MCS encompasses a broad range of chronic polysymptomatic conditions and complaints whose triggers are reported to include low levels of common indoor and outdoor environmental chemicals, such as pesticides and solvents. Other investigators have found evidence of increased prevalence of depression, anxiety, and somatization disorders in MCS patients and have concluded that their psychiatric conditions account for the clinical picture. However, none of these studies has presented any data on the effects of chemicals on symptoms or on objective measures of nervous system function. Synthesis of the MCS literature with large bodies of research in neurotoxicology, occupational medicine, and biological psychiatry, suggests that the phenomenology of MCS patients overlaps that of affective spectrum disorders and that both involve dysfunction of the limbic pathways. Animal studies demonstrate that intermittent repeated low level environmental chemical exposures, including pesticides, cause limbic kindling. Kindling (full or partial) is one central nervous system mechanism that could amplify reactivity to low levels of inhaled and ingested chemicals and initiate persistent affective, cognitive, and somatic symptomatology in both occupational and nonoccupational settings. As in animal studies, inescapable and novel stressors could cross-sensitize with chemical exposures in some individuals to generate adverse responses on a neurochemical basis. The olfactory-limbic model raises testable neurobiological hypotheses that could increase understanding of the multifactorial etiology of MCS and of certain overlapping affective spectrum disorders.
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PMID:An olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationships to kindling and affective spectrum disorders. 142 Jun 41

High-frequency stimulation of the granule cell layer of the olfactory bulb (OB) has previously been shown to result in a selective long-term potentiation (LTP) of late components of potentials evoked in the OB and piriform cortex (PC). The functional impact of this potentiation was explored in male Long-Evans rats with chronically implanted electrodes by comparing the effects of paired-pulse stimulation of the OB in potentiated and control animals. Effects were examined on two components of the potential evoked in the PC: A1, which represents the population EPSP produced by OB mitral cells in PC pyramidal cells via the lateral olfactory tract (LOT), and B1, which represents the subsequent population EPSP produced by PC pyramidal cells in other pyramidal cells. Two separate functional correlates of selective LTP were found. First, there was enhanced paired-pulse depression of B1, indicating increased inhibition of PC pyramidal cells. Second, there was a shift from paired-pulse facilitation to depression of A1, which was accompanied by a decrease in amplitude of the LOT volley, indicating that fewer mitral cells were activated by the stimulation. This shift was most prominent in animals with stimulating electrodes closest to the mitral cell layer, suggesting that it is dependent upon direct stimulation of mitral cell somata. These observations, together with other results reported in the manuscript, support the conclusion that there is an enhanced inhibition of mitral cells following selective LTP. Thus a primary consequence of selective LTP appears to be enhanced inhibition of principal neurons in both the PC and OB. These findings are consistent with our previous proposal that selective LTP represents potentiation at excitatory synapses made by PC pyramidal cells on inhibitory interneurons in the PC and OB.
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PMID:Functional correlates of selective long-term potentiation in the olfactory cortex and olfactory bulb. 151 5

Ablation of olfactory bulbs in rats reduced male sexual behavior, and altered the distribution of wheel-running activity between the light and dark phases of a 12:12 LD photoperiod. These effects were partially reversed by the tricyclic antidepressant amitriptyline. Olfactory bulbectomy also altered serotonin metabolism (5-HIAA/5-HT ratio) in the frontal cortex, nucleus accumbens, hippocampus and corpus striatum. These observations support the hypothesis that olfactory bulbectomy in rodents serves as a model of agitated hyposerotonergic depression.
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PMID:Olfactory bulbectomy as a model for agitated hyposerotonergic depression. 152 54

The distribution of inositol 1,4,5-trisphosphate (InsP3) 3-kinase was studied in the adult rat brain, using polyclonal antibodies raised against the purified 50,000-Da rat brain enzyme by immunohistochemistry and Western blot, in addition to enzymatic assay. Immunohistochemically, the enzyme was detected in neurons, where it was localized in the dendrites and at the periphery of the cell bodies. Using selective toxin lesions, the highest enzyme levels were found in the dendrites of hippocampal CA1 pyramidal cells and in neurons in the dorsal portion of the lateral septum, regions both involved in long-term potentiation; and in the dendrites of Purkinje cell subpopulations in the cerebellum, a region involved in long-term depression. High levels were found in neurons in the cortex; in the anterior olfactory nucleus; in the striatum (caudate, putamen, olfactory tubercle, Calleja islets and accumbens); in the central nucleus of the amygdala; in the hippocampal dentate gyrus and in the subiculum. The enzyme was not detected in other brain regions. By Western blot, a 50,000-Da immunoreactive band was present in the cortex, caudate-putamen and cerebellum. This band was most highly stained in the hippocampus. InsP3 3-kinase activity, stimulated by calcium/calmodulin, corresponded to 6172-2638 pmol of InsP4 produced/min/mg protein in the hippocampus followed by frontal and parietotemporal cortex and cerebellum. This activity was below 400 in the brainstem and spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inositol 1,4,5-trisphosphate 3-kinase distribution in the rat brain. High levels in the hippocampal CA1 pyramidal and cerebellar Purkinje cells suggest its involvement in some memory processes. 164 40

Dose-dependent depression of the electrically evoked surface-negative field potential (N-wave) produced by bath-superfusion of carbachol was measured in guinea-pig olfactory cortex slices maintained in vitro. The possible involvement of M3 (smooth muscle/glandular) type muscarinic receptors in partly mediating this response was investigated by testing the effectiveness of the muscarinic M3 receptor antagonists hexahydro-sila-difenidol (HHSiD) and p-fluoro-hexahydro-sila-difenidol (p-F-HHSiD). Low doses of HHSiD (10-100 nM) or p-F-HHSiD (up to 1 microM), pre-applied for 30 min, produced no obvious antagonism of carbachol responses. However, a clear competitive-type inhibition of carbachol effects was observed in 250 nM-1 microM HHSiD or 10-50 microM p-F-HHSiD respectively. Schild plot analysis (regression slope constrained to unity) of pooled data yielded pA2 values of 6.6 for HHSiD (n = 6 slices) and 5.5 for p-F-HHSiD (n = 6 slices) respectively, suggesting a weak competitive antagonism by both compounds. In addition, combination experiments using either HHSiD or p-F-HHSiD with atropine, produced dose-ratio shifts close to those predicted for two antagonists competing for a common receptor site. By comparison, another suggested M3-receptor antagonist, 4-diphenyl-acetoxy-N-methyl-piperidine methiodide (4-DAMP) was a potent competitive blocker of carbachol responses. Schild analysis for 4-DAMP versus carbachol gave a pA2 of 7.9 (n = 6 slices). It is concluded that the muscarinic receptors involved in the suppression of the olfactory cortical N-wave possess a low affinity for HHSiD and particularly for p-F-HHSiD, but not 4-DAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscarinic inhibition of excitatory neurotransmission in guinea-pig olfactory cortex slices: weak antagonism by M3-muscarinic receptor antagonists. 165 79


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