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)

Intact, pentobarbital anesthetized cats (with and without brainstem stimulating electrode implants) and unanesthetized Sherrington (gamma-driven) decerebrate cats "smoked" cigarettes of varying nicotine content (0.2-2.5 mg). Nicotine free lettuce leaf cigarettes were used as controls. "Smoking doses" of nicotine base (10-25 micrograms/kg) were administered i.v. for comparison. Smoke inhalation produced motor reflex depression which paralleled the nicotine content of the cigarettes "smoked". Patellar reflex facilitation due to mesencephalic reticular stimulation was reduced by doses of nicotine and cigarette smoke. Cigarettes (2.5 mg nicotine) and doses of nicotine (25-50 micrograms/kg, i.v.) significantly reduced rigidity and patellar reflex amplitude in the gamma-decerebrate cat. Dihydro-beta-erythroidine reduced the nicotine and cigarette smoke induced patellar reflex depression but not the diminution in the rigidity. Smoking doses of nicotine suppressed pentobarbital-induced EEG spindles in acutely prepared cats. Nicotine (10-25 micrograms/kg) produced EEG and behavioral arousal in cats with chronic deep electrodes. It was concluded that cigarette smoke produces its pharmacological effects via its nicotine content.
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PMID:Central nervous system responses to cigarette smoke inhalation in the cat. 48 88

1. Studies involving the electrophoretic administration of antagonists of ACh (atropine, DHbetaE) and cholinesterase inhibitors (neostigmine, physostigmine) to MGN neurones indicate that ACh is an excitatory transmitter in the feline MGN, most probably released from fibres which originate in or traverse the mesencephalon.2. Auditory afferents to the MGN, cortico-geniculate fibres and the excitatory fibres which mediate ;spontaneous' firing of MGN neurones are unlikely to be cholinergic.3. Almost all geniculo-cortical relay cells are excited by ACh, this excitation being mediated by receptors which have both muscarinic and nicotinic properties. The excitation of relay cells by ACh is sometimes preceded or followed by a depression of firing which is resistant to atropine and DHbetaE, but the significance of this depression is unknown.4. The firing of many unidentified MGN neurones is depressed by ACh in the absence of any excitation, and this depression is blocked by both atropine and DHbetaE, and potentiated by anticholinesterases. This type of depression by ACh may be related to cholinergic inhibition, but this possibility has yet to be investigated.
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PMID:Cholinergic and non-cholinergic transmission in the medial geniculate nucleus of the cat. 434 15

Activation of neuronal nicotinic acetylcholine receptors (nAChRs) modulates the induction of long-term potentiation (LTP), a possible cellular mechanism for learning. This study was undertaken to determine the effects of activation of nAChRs by nicotine on long-term plasticity in the songbird zebra finch, which is a valuable model to study synaptic plasticity and its implications to behavioral learning. Electrophysiological recordings in the robust nucleus of the archistriatum (RA) in adult zebra finch brain slices reveal that tetanic stimulation alone does not produce LTP. However, LTP is induced by such stimulation in the presence of nicotine. The nicotine-mediated LTP is blocked by dihydro-beta-erythroidine (DHbetaE, 1 microM), an antagonist having a greater effect against nAChRs containing the alpha 4 subunit. In the presence of methyllcaconitine (MLA, 10 nM), an antagonist of nAChRs containing the alpha 7 subunit, a long-term depression (LTD) is unmasked, implicating a bi-directional type of plasticity in the zebra finch RA, which is modulated by differential activation of nAChR subtypes. Intracellular recordings from single neurons show a depression of the afterhyperpolarization (AHP) and an increase in frequency of evoked and spontaneous action potentials in the presence of nicotine. These results suggest that nicotinic cholinergic mechanisms may play a critical role in synaptic plasticity in the zebra finch song system and thereby influence song learning and plasticity.
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PMID:Nicotine-mediated plasticity in robust nucleus of the archistriatum of the adult zebra finch. 1526 10

A role for neuronal nicotinic receptor (NNR) activation in animal models of depression has been established. In order to determine the mechanism by which NNR ligands exert their antidepressant effects, experiments using different NNR receptor antagonists in both the mouse and the rat forced swim test (RFST) were performed. In the mouse forced swim test (MFST), A-85380 (0.62 micromol/kg = 0.14 mg/kg, i.p.), an NNR agonist, increased swim distance when administered 15 min prior to test. This effect was blocked by pre-treatment with mecamylamine (1.5 micromol/kg = 0.3 mg/kg, i.p.), suggesting that an NNR mechanism is involved. Further, chlorisondamine at a non-central nervous system (CNS) penetrating dose (1.6 micromol/kg = 1 mg/kg, i.p.) did not antagonize A-85380 in this model, thus implicating central rather than peripheral nicotinic receptors. Dihydro-beta-erythroidine (DHbetaE, 0.3 micromol/kg = 0.1 mg/kg, i.p.) pre-treatment also blocked this effect, indicating that the alpha4beta2 receptor subtype may be involved in A-85380-induced antidepressant effects. Finally, methiothepin (0.33 micromol/kg = 0.14 mg/kg, i.p.) pre-treatment antagonized this effect, suggesting serotonergic involvement. In the rat modified forced swim test, sub-acute administration of A-85380 (0.62 micromol/kg, i.p.) increased swimming behavior and decreased immobility. Climbing behavior was unaffected. In contrast, desipramine treatment (33 micromol/kg = 10 mg/kg, i.p.) resulted in an increase in climbing behavior with no effect on swimming. This behavioral profile has been shown to be more typical of serotonergic rather than noradrenergic antidepressants, suggesting that A-85380 exerts its effects via NNR activation of serotonergic systems.
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PMID:Mechanism of action of A-85380 in an animal model of depression. 1527 99

While the mechanisms underlying nicotinic acetylcholine receptor (nAChR)-mediated analgesia remain unresolved, one process that is almost certainly involved is the recently-described nicotinic enhancement of inhibitory synaptic transmission in the spinal cord dorsal horn. Despite these observations, the prototypical nicotinic analgesic (epibatidine) has not yet been shown to modulate inhibitory transmission in the spinal cord. Furthermore, while nAChRs have been implicated in short-term modulation, no studies have investigated the role of nAChRs in the modulation of long-term synaptic plasticity of inhibitory transmission in dorsal horn. Whole-cell patch clamp recordings from dorsal horn neurons of neonatal rat spinal cord slices were therefore conducted to investigate the short- and long-term effects of nicotinic agonists on GABAergic transmission. GABAergic synaptic transmission was enhanced in 86% of neurons during applications of 1 microM nicotine (mean increased spontaneous GABAergic inhibitory postsynaptic current (sIPSC) frequency was approximately 500% of baseline). Epibatidine (100 nM) induced an increase to an average of approximately 3000% of baseline, and this effect was concentration dependent (EC50=43 nM). Nicotinic enhancement was inhibited by mecamylamine and DHbetaE, suggesting an important role for non-alpha7 nAChRs. Tetrodotoxin (TTX) did not alter the prevalence or magnitude of the effect of nicotine, but the responses had a shorter duration. Nicotine did not alter evoked GABAergic IPSC amplitude, yet the long-term depression (LTD) induced by strong stimulation of inhibitory inputs was reduced when paired with nicotine. These results provide support for a mechanism of nicotinic analgesia dependent on both short and long-term modulation of GABAergic synaptic transmission in the spinal cord dorsal horn.
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PMID:Nicotinic modulation of GABAergic synaptic transmission in the spinal cord dorsal horn. 1564 48

Approximately 70% of tobacco smokers wish to quit, but attempts are often unsuccessful partly due to the aversive nicotine withdrawal syndrome. We investigated the possible involvement of nicotinic and dopaminergic signalling in the central nucleus of the amygdala (CeA) and dorsolateral bed nucleus of the stria terminalis (dlBNST) in the anhedonic depression-like effect of precipitated nicotine withdrawal in rats. Nicotine-dependent rats exhibit elevations in intracranial self-stimulation (ICSS) thresholds compared to control rats after cessation of chronic nicotine administration (spontaneous withdrawal) or systemic or intra-ventral tegmental area (VTA), but not intra-nucleus accumbens (NAcc), administration of nicotinic acetylcholine receptor (nAchR) antagonists while exposed to nicotine (precipitated withdrawal). We examined whether intracerebral administration of the nAChR antagonist dihydro-beta-erythroidine (DHbetaE; 0.6-20 microg total bilateral dose) or the dopamine D1-like receptor antagonist SCH 23390 (2-16 microg total bilateral dose) into the CeA and dlBNST results in withdrawal-like threshold elevations in nicotine-treated rats. Nicotinic acetylcholine and D1-like receptor blockade in the CeA or the dlBNST did not induce differential threshold elevations in nicotine- and saline-treated rats. Further, the highest SCH 23390 dose (16 microg bilateral dose) injected into the dlBNST, but not the CeA, elevated thresholds similarly in both saline- and nicotine-treated rats, suggesting that dopaminergic signalling in the dlBNST may regulate brain reward function under baseline conditions. These results suggest that nACh and D1-like signalling in the CeA and the dlBNST does not develop neuroadaptations with the development of nicotine dependence that may be involved in the depression-like aspects of nicotine withdrawal.
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PMID:Blockade of nicotinic acetylcholine or dopamine D1-like receptors in the central nucleus of the amygdala or the bed nucleus of the stria terminalis does not precipitate nicotine withdrawal in nicotine-dependent rats. 1656 23

This study aims to clarify how endogenous release of cortical acetylcholine (ACh) modulates the balance between excitation and inhibition evoked in visual cortex. We show that electrical stimulation in layer 1 produced a significant release of ACh measured intracortically by chemoluminescence and evoked a composite synaptic response recorded intracellularly in layer 5 pyramidal neurons of rat visual cortex. The pharmacological specificity of the ACh neuromodulation was determined from the continuous whole-cell voltage clamp measurement of stimulation-locked changes of the input conductance during the application of cholinergic agonists and antagonists. Blockade of glutamatergic and gamma-aminobutyric acid (GABAergic) receptors suppressed the evoked response, indicating that stimulation-induced release of ACh does not directly activate a cholinergic synaptic conductance in recorded neurons. Comparison of cytisine and mecamylamine effects on nicotinic receptors showed that excitation is enhanced by endogenous evoked release of ACh through the presynaptic activation of alpha(*)beta4 receptors located on glutamatergic fibers. DHbetaE, the selective alpha4beta2 nicotinic receptor antagonist, induced a depression of inhibition. Endogenous ACh could also enhance inhibition by acting directly on GABAergic interneurons, presynaptic to the recorded cell. We conclude that endogenous-released ACh amplifies the dominance of the inhibitory drive and thus decreases the excitability and sensory responsiveness of layer 5 pyramidal neurons.
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PMID:Involvement of nicotinic and muscarinic receptors in the endogenous cholinergic modulation of the balance between excitation and inhibition in the young rat visual cortex. 1917 36