Dual effects of morphine on spontaneous seizure activity in mouse brain hippocampal slices

Opiates have complex effects on seizure activity. They have both anti- and proconvulsive effects depending on experimental conditions. The aim of this study was to determine the effects of different doses of morphine and naloxon on spontaneous seizure activity in mouse brain hippocampal slices. Spontaneous epileptic activity in the brain hippocampal slices of mouse was induced by continuous perfusion of low magnesium artificial cerebrospinal fluid [low -Mg[2+] ACSF]. Extra cellular recordings were performed in the hippocampal CA1 pyramidal cell layer to account for the effects of the drugs on amplitude, duration and number of the ictal events as well as number of interictal spikes. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration [10 microM], morphine decreased seizure activity. Higher morphine concentrations [30 and 100 microM] enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist, blocked the proconvulsant action of morphine. The results of this study showed that the effect of morphine on seizure in mouse is dose dependent. In other words, low systemic doses of morphine have anticonvulsant effects while high doses are proconvulsant

[Dual effects of morphine on spontaneuse seizure activity in mouse brain hippocampal slices]

Opiates have complex effects on seizure activity. They have both anti-and proconvulsive effects depending on experimental conditions. The aim of this study was to determine the effects of different doses of morphine and naloxon on spontaneous seizure activity in mouse brain hippocampal slices. Spontaneous epileptic activity in the brain slices of mouse was induced by continuous perfusion of low magnesium artificial cerebrospinal fluid [low-Mg2+ACSF]. Extra cellular recordings were performed in the hippocampal CA1 pyramidal cell layer to account for the effects of the drugs on amplitude, duration and number of the ictal events as well as number of interictal spikes. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration [10 micro M], morphine decreased seizure activity. Higher morphine concentrations [30 and 100 micro M] enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist, blocked the proconvulsant action of morphine. The results of this study showed that the effect of morphine on seizure in mouse is dose dependent. In other words, low systemic doses of morphine have anticonvulsant effects while high doses are proconvulsant

[Effects of dark rearing on clonic seizure threshold and pentyleneterazol induced epileptiform activity in mice]

Epileptic seizures are generally considered as complex and abnormal hyperexcitable phenomena in the brain. Probable changing of excitability in visual cortex by dark rearing [DR] might lead to clonic seizure. In this study the possible effect of dark rearing on Pentylenetetrazol [PTZ] induced generalized clonic seizure was studied. To assess the generalized clonic seizures [GCS] threshold and incidence and latency of GCS, 0.5% Pentylenetetrazol was administrated intravenously and 80 mg/kg subcutaneously to the control and dark reared animals. Our results showed that generalized clonic seizure threshold in DR group was not changed but occurring of GCS in DR animals was significantly lower and its latency was higher than the control animals. The tonic- clonic seizure was not different between the two groups. In spite of increasing seizure susceptibility in visual cortex by light deprivation, a kind of protection was observed in dark reared animals. Further studies seem to be necessary to elucidate the role of other factors such as melatonin

[ role of estrogen on cardiovascular response due to GABA and glutamate receptors in Rostral ventromedial medulla in ovarictomized rats]

The Rostral Ventromedial Medulla [RVMM] is one of the nuclei controlling cardiovascular system. This study was performed to determine the effects of 17beta-estradiol [E], on the GABA and Glutamate cardiovascular responses of RVMM of female rats. Experiments were performed on 40 anaesthetized and paralyzed rats, divided into two groups of ovarictomized [OVX] and ovarictomized-estrogen treated [OVX+E] rats. Drugs [50 nl] bicuculline methiodide [BMI] an antagonist GABAA receptor [1 mM], phaclophen an antagonist GABAA receptor [5mM], and kynurenic acid a nonselective antagonist glutamate receptors [5 mM], were microinjected by micropipette into the RVMM using stereotaxic system. Blood pressure and heart rate were recorded before and throughout each experiment. The means of maximum changes of mean arterial pressure and heart rate were compared between groups of OVX and OVX+E and saline using ANOVA. In the OVX+E group, estrogen decreased the mean arterial blood pressure [P<0.05] and heart rate [P<0.001] compared to those of OVX group. Microinjection of BMI resulted in an increase of heart rate [HR] with no significant effect on the blood pressure [BP] in both OVX and OVX+E, but the increase of HR was significantly higher than in the OVX+E group [p<0.05]. Microinjection of phaclophen and kynurenic acid had no significant effect on HR and BP in either the OVX or the OVX+E group; not did microinjection of saline have any significant effects on HR and BP. The present data suggest that estrogen decreased the mean arterial blood pressure and heart rate, and in the RVMM of female rats augments the inhibitory effect of the GABAergic system on the heart rate via the GABAA receptors

[ effect of reversible locus coeruleus [LC] on i.v self-administration of morphine and morphine withdrawal syndrome[MWS] signs in rats]

Locus coeruleus [LC] has been hypothesized to play an important role in a variety of behaviors and opiate withdrawal. This study was designed to determine the effects of reversible inactivation of LC on self-administration of morphine and morphine- withdrawal syndrome signs [MWS]. 24 male rats [250-300gr] were surgically implanted bilaterally with cannula in LC then implanted with catheters in the right jugular vein. The rats were tested in 2 groups:Control[saline] and morphine. Morphine group was divided into 3 subgroups: control, sham-operated and LC-inactivated group where they received 1microL 2% Lidocaine 5 minutes prior to testing. Animals were allowed to self-administer morphine [1mg/infusion] during 10 consecutive days for 2 hours. The number of lever pressing was recorded. At the end of the training day all groups received naloxone [2mg/kg I.P] and MWS were studied for 30 minutes. LC inactivation prevents the development of tolerance and dependence on morphine and greatly attenuates morphine-withdrawal syndrome. LC inactivation not only attenuates morphine withdrawal syndrome but also prevents morphine tolerance and dependence in rats