Early Changes in Prodynorphin mRNA and ir‐Dynorphin A Levels after Kindled Seizures in the Rat

Romualdi, Patrizia; Donatini, A.; Bregola, Gianni; Bianchi, Clementina; Beani, L.; Ferri, Sergio Solbes; Simonato, Michele

doi:10.1111/j.1460-9568.1995.tb00705.x

Cited by 20 publications

(11 citation statements)

References 30 publications

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“…The supernatants were removed and stored at -201C. Dynorphin A tissue immunoreactivity was measured with a specific radioimmunoassay as previously described (Romualdi et al, 1995). …”

Section: Biochemical Assaysmentioning

confidence: 99%

Chronic Δ9-Tetrahydrocannabinol During Adolescence Provokes Sex-Dependent Changes in the Emotional Profile in Adult Rats: Behavioral and Biochemical Correlates

Rubino

Viganò

Realini

et al. 2008

Neuropsychopharmacol

304

303

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Few and often contradictory reports exist on the long-term neurobiological consequences of cannabinoid consumption in adolescents. The endocannabinoid system plays an important role during the different stages of brain development as cannabinoids influence the release and action of different neurotransmitters and promote neurogenesis. This study tested whether long-lasting interference by cannabinoids with the developing endogenous cannabinoid system during adolescence caused persistent behavioral alterations in adult rats. Adolescent female and male rats were treated with increasing doses of D 9 -tetrahydrocannabinol (THC) for 11 days (postnatal day (PND) 35-45) and left undisturbed until adulthood (PND 75) when behavioral and biochemical assays were carried out. CB1 receptor level and CB1/G-protein coupling were significantly reduced by THC exposure in the amygdala (Amyg), ventral tegmental area (VTA) and nucleus accumbens (NAc) of female rats, whereas male rats had significant alterations only in the amygdala and hippocampal formation. Neither female nor male rats showed any changes in anxiety responses (elevated plus maze and open-field tests) but female rats presented significant 'behavioral despair' (forced swim test) paralleled by anhedonia (sucrose preference). In contrast, male rats showed no behavioral despair but did present anhedonia. This different behavioral picture was supported by biochemical parameters of depression, namely CREB alteration. Only female rats had low CREB activity in the hippocampal formation and prefrontal cortex and high activity in the NAc paralleled by increases in dynorphin expression. These results suggest that heavy cannabis consumption in adolescence may induce subtle alterations in the emotional circuit in female rats, ending in depressive-like behavior, whereas male rats show altered sensitivity to rewarding stimuli.

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“…The supernatants were removed and stored at -201C. Dynorphin A tissue immunoreactivity was measured with a specific radioimmunoassay as previously described (Romualdi et al, 1995). …”

Section: Biochemical Assaysmentioning

confidence: 99%

Chronic Δ9-Tetrahydrocannabinol During Adolescence Provokes Sex-Dependent Changes in the Emotional Profile in Adult Rats: Behavioral and Biochemical Correlates

Rubino

Viganò

Realini

et al. 2008

Neuropsychopharmacol

304

303

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“…Dynorphin release in the hippocampus, as measured by microdialysis, is increased during seizures induced by amygdaloid kindling in rats (Rocha et al 1997). On the other hand, dynorphin protein expression is reduced in hippocampus tissue following seizures induced by amygdaloid kindling (McGinty et al 1986; Romualdi et al 1995). Seizures induced by kainic acid (KA) also result in a reduction in dynorphin immunoreactivity in the hippocampus of rats 6 h after KA administration (Kanamatsu et al 1986), and also in mice 4 days after KA (Gall, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…The paradox of the increased release followed by a decrease in protein expression is thought to be caused by enhanced dynorphin release and, possibly, depletion during the seizures. Expression of prodynorphin mRNA is increased in the hippocampus of rats, for at least 24 h after a seizure induced by KA (Douglass et al 1991; Lason et al 1992) and at least 60 min after a seizure induced by amygdaloid kindling (Romualdi et al 1995), possibly to account for the protein depletion during seizures. It is thought that dynorphin released during seizures acts to limit the spread of excitability, and there is a significant amount of evidence to suggest that it acts as an anticonvulsant.…”

Section: Introductionmentioning

confidence: 99%

Activation of κ opioid receptors increases intrinsic excitability of dentate gyrus granule cells

McDermott

Schrader

2011

The Journal of Physiology

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Non-technical summaryThe hippocampus is an area of the brain that is important for learning and memory and a locus for hyperexcitable activity, such as epilepsy. The dentate gyrus (DG) of the hippocampus controls information flow into the rest of the hippocampus, and thus provides protection from excess activity. Under pathological conditions, such as epilepsy, this protective feature is circumvented and uninhibited activity flows throughout the hippocampus. Activation of kappa (κ) opioid receptors (KORs) prevents both the behavioural and electroencephalographic measures of seizures in several models of epilepsy, and other complex behaviours such as stress-induced deficits in learning. Understanding the cellular effect of KOR activation is critical to our understanding of DG function. In this study we show that, contrary to our hypothesis, activation of the KORs increases excitability of the DG cells. These results suggest that regulation of activity in the DG by activation of KORs is more complex than previously thought.Abstract The dentate gyrus of the hippocampus is thought to control information flow into the rest of the hippocampus. Under pathological conditions, such as epilepsy, this protective feature is circumvented and uninhibited activity flows throughout the hippocampus. Many factors can modulate excitability of the dentate gyrus and ultimately, the hippocampus. It is therefore of critical importance to understand the mechanisms involved in regulating excitability in the dentate gyrus. Dynorphin, the endogenous ligand for the kappa (κ) opioid receptor (KOR), is thought to be involved in neuromodulation in the dentate gyrus. Both dynorphin and its receptor are widely expressed in the dentate gyrus and have been implicated in epilepsy and other complex behaviours such as stress-induced deficits in learning and stress-induced depression-like behaviours. Administration of KOR agonists can prevent both the behavioural and electroencephalographic measures of seizures in several different models of epilepsy. Antagonism of the KORs also prevents stress-induced behaviours. This evidence suggests the KORs as possible therapeutic targets for various pathological conditions. In addition, KOR agonists prevent the induction of LTP. Although there are several mechanisms through which dynorphin could mediate these effects, no studies to date investigated the effects of KOR activation on intrinsic membrane properties and cell excitability. We used whole-cell, patch-clamp recordings from acute mouse hippocampus slices to investigate the effect of KOR activation on dentate gyrus granule cell excitability. The agonist U69,593 (U6, 1 μM) resulted in a lower spike threshold, a decreased latency to first spike, an increased spike half-width, and an overall increase in spike number with current injections ranging from 15 to 45 pA. There was also a reduction in the interspike interval (ISI) both early and late in the spike train, with no change in membrane potential or input resistance. Preincubation of the slice with the se...

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“…Dynorphin hat eine hohe Affinität für den j-Opioidrezeptor. In Tiermodellen des Status epilepticus wurde meist eine anfängliche Reduktion, später eine erhöhte Expression der Dynorphin-mRNA beobachtet [7,8,11,15,18,20,33,40,41,57]. Der Anstieg der Immunreaktivität in der inneren Molekularschicht bei TLE-Patienten mit Hippokampussklerose kommt wahrscheinlich durch das "sprouting" von Dynorphin-haltigen Moosfasern zustande (Abb.…”

Section: Plastic Changes Of Neuropeptides In Patients With Temporal Lunclassified

Plastische Ver�nderungen von Neuropeptiden bei Patienten mit Temporallappenepilepsie

Pirker

Czech

Baumgartner

et al. 2003

Zeitschrift f�r Epileptologie

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Plastic changes of neuropeptides in patients with temporal lobe epilepsyn Abstract Neuropeptides are stored together with the classical neurotransmitter in large dense core vesicles from where they are released upon stimulation. In animal models, neuropeptides have been shown to influence neuronal excitability. For example, an anticonvulsive action was found for neuropeptide Y (NPY), galanin, dynorphin and somatostatin. By contrast, substance P was found to have a proconvulsive action. We investigated the expression of NPY, dynorphin, secretoneurin and chromogranin B in hippocampi from patients with intractable temporal lobe epilepsy (TLE) (n = 29; mean age = 34.5 years; mean duration of epilepsy = 21.4 years) and post mortem controls (n = 21; mean age = 57.7 years; mean post mortem delay = 17.2 hours). In situ hybridization for dynorphin showed a marked increase of mRNA expression in granule cells of the dentate gyrus. For NPY, we found increased mRNA expression in hilar interneurons. Immunohistochemical staining showed a sprouting of neuropeptide-containing axons. Antibodies for dynorphin, secretoneurin and chromogranin B labeled mossy fiber terminals in the inner molecular layer of the denate gyrus of patients with, but not without, hippocampal sclerosis. NPY-and secretoneurin-containing interneurons revealed a dense plexus of fibers in the molecular layer and the hilus of the dentate gyrus as well as in stratum lucidum, the terminal field of mossy fibers. Radioligand binding to the NPY Y2 receptor, which mediates anticonvulsive actions of NPY, was increased in the hippocampus of TLE patients. In summary, our data show a marked reorganization of hippocampal circuits and an upregulation of the expression of dynorphin, NPY and the Y2 receptor in the epileptic hippocampus. These changes may contribute to endogenous anticonvulsive mechanisms in TLE patients.

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Early Changes in Prodynorphin mRNA and ir‐Dynorphin A Levels after Kindled Seizures in the Rat

Cited by 20 publications

References 30 publications

Chronic Δ9-Tetrahydrocannabinol During Adolescence Provokes Sex-Dependent Changes in the Emotional Profile in Adult Rats: Behavioral and Biochemical Correlates

Chronic Δ9-Tetrahydrocannabinol During Adolescence Provokes Sex-Dependent Changes in the Emotional Profile in Adult Rats: Behavioral and Biochemical Correlates

Activation of κ opioid receptors increases intrinsic excitability of dentate gyrus granule cells

Plastische Ver�nderungen von Neuropeptiden bei Patienten mit Temporallappenepilepsie

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