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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opioid peptides effects on neural membrane as well as neural responses evoked by sensory stimuli with different modality and site of application, were investigated in L-RPII command neurones of defensive behaviour of semi-intact preparation in the land snail Helix lucorum. Met-enkephalin (10 uM) application onto the snail CNS increases membrane excitability and produces facilitation of neural responses evoked by quinine solution (0.5%) application onto snail head and depression of reactions evoked by tactile stimulation of the head. Met-enkephalin in dose of 0.1 uM initiates only a depression of neural responses evoked by tactile stimulation of the head. Leu-enkephalin (10 uM) application suppresses neural reactions evoked by tactile stimulation of the head. Membrane excitability and neural responses evoked by quinine application onto the snail head do not change after leu-enkephalin administration. Effects appear 10-20 min after initiation of the peptide application. Initial neural responses were observed 15-30 min after CNS washing with Ringer solution. In addition, facilitation of neural responses evoked by chemical stimulation of the snail head was found 30-50 min after leu-enkephalin washing. Peptides do not change neural responses evoked by tactile stimulation of the snail foot. Neural effects of peptides were prevented by simultaneous naloxon administration (50 uM). Experimental results show selective opioid peptides' effects on excitability and plasticity of L-RPII neural inputs with site- and modality-specifics.
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PMID:[Selectivity of opioid peptide effects on excitability and various sensory inputs in LPl1 and PPl1 command neurons participating in defensive behavior of the snail Helix lucorum]. 1186 57

Synaptic adaptations are thought to be an important component of the consequences of drug abuse. One such adaptation is an up-regulation of adenylyl cyclase that has been shown to increase transmitter release at several inhibitory synapses. In this study the effects of chronic morphine treatment were studied on mossy fiber synapses in the guinea pig hippocampus using extracellular field potential recordings. This opioid-sensitive synapse was chosen because of the known role of the adenylyl cyclase cascade in the regulation of glutamate release. Long-term potentiation (LTP) at the mossy fiber synapse was enhanced after chronic morphine treatment. In control animals, opioid antagonists increased LTP but had no effect in morphine-treated guinea pigs. In contrast, the long-lasting depression of transmission induced by a mGluR agonist and CA1 LTP were not altered. Chronic morphine treatment neither caused tolerance to mu- and kappa-receptor-mediated inhibition at the mossy fiber synapse nor modified total hippocampal dynorphin levels. The results suggest that the phasic inhibition of glutamate transmission mediated by endogenous opioids is reduced after chronic exposure to morphine.
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PMID:Chronic morphine treatment alters endogenous opioid control of hippocampal mossy fiber synaptic transmission. 1197 83

The cAMP response element-binding protein (CREB) is a critical integrator of neural plasticity that is responsive in a brain region-specific manner to a variety of environmental and pharmacological stimuli, including widely prescribed antidepressant medications. We developed inducible transgenic lines of mice that express either CREB or a dominant-negative mutant of CREB (mCREB) in forebrain regions and used these mice to determine the functional significance of this transcription factor in the learned helplessness paradigm, a behavioral model of depression. We also use a complementary viral-mediated gene transfer approach to directly test the effect of mCREB in the nucleus accumbens, a brain region important for motivation and reward. The results demonstrate that blockade of CREB by overexpression of mCREB in transgenic mice or by viral expression of mCREB in the nucleus accumbens produces an antidepressant-like effect, whereas overexpression of CREB in transgenic mice results in the opposite phenotype. In addition, mCREB expression was colocalized with and decreased the expression of prodynorphin in nucleus accumbens medium spiny neurons, and antagonism of dynorphin in the nucleus accumbens was sufficient to produce an antidepressant-like effect similar to that observed after blockade of CREB. Together, the results demonstrate that nucleus accumbens CREB-dynorphin influence behavior in the learned helplessness model and suggest that this signaling cascade may contribute to symptoms of depression.
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PMID:Inhibition of cAMP response element-binding protein or dynorphin in the nucleus accumbens produces an antidepressant-like effect. 1248 82

We showed previously that cAMP response element-binding protein (CREB) within the nucleus accumbens (NAc) of rats regulates immobility in the forced swim test (FST), an assay used to study depression. Because CREB regulates expression of dynorphin (which acts at kappa-opioid receptors) in NAc neurons, these findings raised the possibility that kappa-receptors mediate immobility behaviors in the FST. Here, we report that i.c.v. administration of the kappa-antagonist nor-binaltorphimine dose dependently decreased immobility in the FST, suggesting that it has antidepressant-like effects. Implicating a specific effect at kappa-receptors, similar antidepressant-like effects were seen after treatment with either of two novel, structurally dissimilar kappa-antagonists: 5'-guanidinonaltrindole, which was effective after i.c.v. but not systemic treatment, and 5'-acetamidinoethylnaltrindole (ANTI), which was potent and effective after systemic treatment. The behavioral effects of the kappa-antagonists resembled those of tricyclic antidepressants (desipramine) and selective serotonin reuptake inhibitors (fluoxetine and citalopram). Conversely, systemic administration of the kappa-agonist [5alpha,7alpha,8beta]-N-methyl-N-[7-[1-pyrrolidinyl]-1-oxaspiro[4.5]dec8-yl]-benzenacetamide (U-69593) dose dependently increased immobility in the FST, consistent with prodepressant-like effects. The effects of the kappa-ligands in the FST were not correlated with nonspecific effects on locomotor activity. Furthermore, the most potent and effective kappa-antagonist (ANTI) did not affect the rewarding impact of lateral hypothalamic brain stimulation at a dose with strong antidepressant-like effects. These findings are consistent with the hypothesis that CREB-mediated induction of dynorphin in the NAc "triggers" immobility behavior in the FST. Furthermore, they raise the possibility that kappa-antagonists may have efficacy as antidepressants, but lack stimulant or reward-related effects.
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PMID:Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. 1264 85

The modulatory effects of methionine-enkephalin (M-ENK) and selective opioid-receptor agonists on GABA-activated whole-cell currents were investigated in neurons acutely dissociated from the superficial laminae of the rat spinal dorsal horn using nystatin-perforated patch recording configuration under voltage-clamp conditions. The results show that: (1). GABA acted on GABA(A) receptors and elicited inward Cl(-) currents (I(GABA)) at -60 mV; (2). M-ENK depressed I(GABA) in approximately 65% of the tested neurons and potentiated I(GABA) in approximately 15% of the neurons tested; (3). the agonists of mu-, kappa-, and delta-opioid receptors-[D-AIa(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), dynorphin-A (Dyn-A), and [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE) also depressed the I(GABA), and the order of agonist potency was DAMGO>Dyn-A>DPDPE; and (4) naloxone blocked the inhibitory effects of M-ENK on I(GABA). The antagonists of mu-, kappa-, and delta-opioid receptors-beta-funaltrexamine (beta-FNA), nor-binaltorphimine (nor-BNI), and naltrindole (NTI) prevented the DAMGO-, Dyn-A-, and DPDPE-induced depression of I(GABA). The results suggest that M-ENK downregulates I(GABA) principally through mu- and kappa-opioid receptors, and thus exerts its modulating effects indirectly on the transmission of noxious information at the spinal level.
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PMID:Opioid peptides modulate the response of neurons of the superficial laminae of the rat spinal dorsal horn to GABA. 1289 84

The nature of the effects of opioid peptides on the properties of electrogenic membranes and the responses of defensive behavior command neurons LPl1 and RPl1, evoked by sensory stimuli of different modalities and application sites was studied in semi-intact preparations from common snails. Application of met-enkephalin (10 microM) to the snail CNS produced increases in membrane excitability along with facilitation of responses to application of dilute quinine solution to the animal's head and depression of responses to tactile stimulation of the head. Met-enkephalin (0.1 microM) produced only depression of responses to tactile stimulation of the head. Application of leu-enkephalin (10 microM) was accompanied by depression of responses to tactile stimulation of the head. Membrane excitability and responses to chemical sensory stimulation during application showed no change during application of this peptide. These effects of both peptides appeared 10-20 min from the start of application and lasted 15-30 min after washing was started. In addition, facilitation of the responses of neurons to chemical sensory stimulation was seen 30-50 min after the start of leu-enkephalin application. The responses of neurons to tactile stimulation of the snail's foot were not altered by application of peptides. The neuronal effects of peptides were suppressed by simultaneous application of naloxone (50 microM). Thus, we observed the selective action of opioid peptides on the synaptic plasticity of neurons LPl1 and RPl1, both in relation to the location of sensory stimulation and in relation to sensory modality.
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PMID:The selective action of opioid peptides on excitability and the various sensory inputs of defensive behavior command neurons LPl1 and RPl1 of the common snail. 1292 Nov 75

The dentate gyrus is believed to play a key role in the pathogenesis of temporal lobe epilepsy. In normal brain the dentate granule cells serve as a high-resistance gate or filter, inhibiting the propagation of seizures from the entorhinal cortex to the hippocampus. The filtering function of the dentate gyrus depends in part on the near absence of monosynaptic connections among granule cells. In humans with temporal lobe epilepsy and in animal models of temporal lobe epilepsy, dentate granule cells form an interconnected synaptic network associated with loss of hilar interneurons. This recurrent mossy fiber pathway mediates reverberating excitation that can reduce the threshold for granule cell synchronization. Factors that augment activity in this pathway include modest increases in [K+]o; loss of GABA inhibition; short-term, frequency-dependent facilitation (frequencies of 1-2 Hz); feedback activation of kainate autoreceptors; and release of zinc from recurrent mossy fiber boutons. Factors that diminish activity include short-term, frequency-dependent depression (frequencies < 1 Hz); feedback activation of type II metabotropic glutamate receptors; and the potential release of GABA, neuropeptide Y, adenosine, and dynorphin from recurrent mossy fiber boutons. The axon sprouting and reactive synaptogenesis that follow seizure-related brain damage can also create or strengthen recurrent excitation in other brain regions. These changes are expected to facilitate participation of these regions in seizures. Thus, reactive processes that are often considered important for recovery of function after most brain injuries probably contribute to neurological dysfunction in epilepsy.
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PMID:The recurrent mossy fiber pathway of the epileptic brain. 1458 19

Rats exposed to learned helplessness (LH), an animal model of depression, showed a recovery following an intracerebroventricular injection of nor-binaltorphimine dihydrochloride (norBNI; a kappa-opioid antagonist). To investigate the potential role of dynorphin A and dynorphin B, we examined the effects of different stress/depression models on dynorphin A and dynorphin B immunoreactivity in hippocampus and nucleus accumbens (NAc). Immobilization stress (3 h) caused an increase in levels of dynorphin A and dynorphin B immunoreactivity in the hippocampus and the NAc. Forced swim stress also temporally increased dynorphin A levels in the hippocampus. Furthermore, exposure to LH produced a similar increase in dynorphin A and dynorphin B in the hippocampus and NAc. Infusions of norBNI into the dentate gyrus or CA3 regions of hippocampus and into the shell or core regions of NAc produced antidepressant-like effects in the LH paradigm. The degrees of norBNI's effects were stronger in the CA3 region and NAc shell and less effective in the dentate gyrus of hippocampus and NAc core. These results indicate that both dynorphin A and dynorphin B contribute to the effects of stress, and suggest that blockade of kappa-opioid receptors may have therapeutic potential for the treatment of depression.
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PMID:Stress increases dynorphin immunoreactivity in limbic brain regions and dynorphin antagonism produces antidepressant-like effects. 1531 81

A common trait of antidepressant drugs, electroconvulsive treatment and physical exercise is that they relieve depression and up-regulate neurotrophic factors as well as cell proliferation and neurogenesis in the hippocampus. In order to identify possible biological underpinnings of depression and the antidepressant effect of running, we analysed cell proliferation, the level of the neurotrophic factor BDNF in hippocampus and dynorphin in striatum/accumbens in 'depressed' Flinders Sensitive Line rats (FSL) and Flinders Resistant Line (FRL) rats with and without access to running-wheels. The FRL strain exhibited a higher daily running activity than the FSL strain. Wheel-running had an antidepressant effect in the 'depressed' FSL rats, as indicated by the forced swim test. In the hippocampus, cell proliferation was lower in the 'depressed' rats compared to the control FRL rats but there was no difference in BDNF or dynorphin levels in striatum/accumbens. After 5 wk of running, cell proliferation increased in FSL but not in FRL rats. BDNF and dynorphin mRNA levels were increased in FRL but not to the same extent in the in FSL rats; thus, increased BDNF and dynorphin levels were correlated to the running activity but not to the antidepressant effect of running. The only parameter that was associated to basal level of 'depression' and to the antidepressant effect was cell proliferation in the hippocampus. Thus, suppression of cell proliferation in the hippocampus could constitute one of the mechanisms that underlie depression, and physical activity might be an efficient antidepressant.
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PMID:The antidepressant effect of running is associated with increased hippocampal cell proliferation. 1576 1

The Flinders sensitive line (FSL) rat is a proposed genetic hypercholinergic animal model of human depression. Considering the strong comorbidity between depression and cocaine dependence we investigated the well-documented behavioral and molecular effects of cocaine in the FSL and their control Flinders resistant line (FRL) rats. First, we found no difference between the two lines to establish cocaine self-administration; both lines reached stable responding within 10 days of training at a fixed ratio-1 schedule of reinforcement (1.5 mg/kg/injection). However, the FSL rats exhibited reduced cocaine intake at a dose of 0.09 mg/kg/injection in a within-session dose-response curve (0.02, 0.09, 0.38, 1.5 mg/kg/injection). Second, we examined the effects of repeated cocaine administration on locomotor activity, dopamine overflow and striatal prodynorphin mRNA expression. We found the FSL rats to be low responders to novelty and to exhibit less locomotor activation after repeated cocaine administration (30 mg/kg, i.p., daily injections for 10 days) than their controls. Microdialysis sampling from the nucleus accumbens shell revealed no significant difference in the dopamine overflow between the rat lines, neither during baseline nor after cocaine stimulation. Postmortem analyses of striatal prodynorphin mRNA expression (using in situ hybridization histochemistry) revealed a differentiated response to the cocaine exposure. In contrast to control FRL rats, the FSL rats showed no typical cocaine-evoked elevation of prodynorphin mRNA levels in rostral subregions of the striatum whereas both strains expressed increased prodynorphin mRNA levels in the caudal striatum after cocaine administration. In conclusion, the FSL animal model of depression demonstrates marked blunting of the locomotor and dynorphin neuroadaptative responses to cocaine in accordance with its enhanced cholinergic sensitivity.
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PMID:Blunted response to cocaine in the Flinders hypercholinergic animal model of depression. 1585 18


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