Differential roles of mGlu(7) and mGlu(8) in amygdala-dependent behavior and physiology.

Glutamate transmission and synaptic plasticity in the amygdala are essential for the learning and expression of conditioned fear. Glutamate activates both ionotropic glutamate receptors and eight subtypes of metabotropic glutamate receptors (mGlu1-8). In the present study, we investigated the roles of mGlu7 and mGlu8 in amygdala-dependent behavior and synaptic plasticity.

Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.

Links between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and persistent fear after single-trial associative learning.

The selective nicotinic acetylcholine receptor alpha7 agonist JN403 is active in animal models of cognition, sensory gating, epilepsy and pain.

Several lines of evidence suggest that the nicotinic acetylcholine receptor alpha7 (nAChR alpha7) is involved in central nervous system disorders like schizophrenia and Alzheimer's disease as well as in inflammatory disorders like sepsis and pancreatitis. The present article describes the in vivo effects of JN403, a compound recently characterized to be a potent and selective partial nAChR alpha7 agonist. JN403 rapidly penetrates into the brain after i.

The rostral anterior cingulate cortex modulates the efficiency of amygdala-dependent fear learning.

Background: The rostral anterior cingulate cortex (rACC) and the amygdala consistently emerge from neuroimaging studies as brain regions crucially involved in normal and abnormal fear processing. To date, however, the role of the rACC specifically during the acquisition of auditory fear conditioning still remains unknown. The aim of this study is to investigate a possible top-down control of a specific rACC sub-region over amygdala activation during pavlovian fear acquisition.

The rostral anterior cingulate cortex modulates depression but not anxiety-related behaviour in the rat.

A growing body of functional imaging studies suggests that human depression and anxiety symptoms are associated with functional abnormalities in the circuitry formed by the rostral anterior cingulate cortex (rACC) and its direct limbic and paralimbic connections. In rodents however, the role of the rACC (rCG1/rCG2) remains unknown in depression-related behaviours and elusive in acute anxiety. In order to address this, we specifically lesioned the rat rCG1/rCG2, and assessed the behavioural outcome using a modified forced swim test (FST) and the elevated plus maze (EPM), tests for depression and anxiety related behaviours respectively.

Ions and amino acid analysis of Cyperus articulatus L. (Cyperaceae) extracts and the effects of the latter on oocytes expressing some receptors.

Extracts from rhizomes of Cyperus articulatus L. (Cyperaceae) used in Africa and Amazonia to treat many diseases has been shown to possess sedative and anticonvulsant properties. The aim of this study is to determine the mechanism of action of Cyperus articulatus extracts.

Effects of subchronic clozapine treatment on long-term potentiation in rat prefrontal cortex.

Several studies postulated an interaction of clozapine with N-methyl-D-aspartate (NMDA) receptor-mediated transmission. We previously showed that acute clozapine application on rat prefrontal cortex (PFC) slices increased NMDA receptor-dependent long-term potentiation (LTP) in the prelimbic (PL) area. The present study explores the effects of subchronic clozapine treatment on LTP in the same brain area.

Anticonvulsant activity of Mimosa pudica decoction.

The decoction of Mimosa pudica leaves given intraperitoneally at dose of 1000-4000 mg/kg protected mice against pentylentetrazol and strychnine-induced seizures. M. pudica had no effect against picrotoxin-induced seizures It also antagonized N-methyl-D-aspartate- induced turning behavior.

Electrophysiological studies on the hippocampus and prefrontal cortex assessing the effects of amyloidosis in amyloid precursor protein 23 transgenic mice.

In vitro and in vivo electrophysiological studies were done to investigate the neuronal function of the hippocampus and prefrontal cortex in the amyloid precursor protein (APP) 23 transgenic mouse model for amyloidosis developed by Sturchler-Pierrat et al. [Proc Natl Acad Sci USA 94 (1997) 13287]. Brain slices were taken from 3, 6, 9, 12, 18 and 24 month old wildtype and hemizygous type APP23 mice.

Differential effects of iloperidone, clozapine, and haloperidol on working memory of rats in the delayed non-matching-to-position paradigm.

Rationale: Because cognitive function, particularly working memory (WM), is severely impaired in schizophrenia, evaluation of neuroleptic medication should include investigation of possible effects on cognition. Iloperidone is a promising, novel atypical neuroleptic drug (NL), for which no cognitive data is presently available.

Objective: To investigate whether the novel atypical NL iloperidone would affect performance of rats on a WM test, using a delayed non-matching-to-position (DNMTP) paradigm, and compare its effects with those of the atypical NL clozapine and the typical NL haloperidol.

Effects of clozapine, haloperidol and iloperidone on neurotransmission and synaptic plasticity in prefrontal cortex and their accumulation in brain tissue: an in vitro study.

The mode of action of the antipsychotic drugs clozapine, haloperidol and iloperidone was investigated in layer V of prefrontal cortex slices using extracellular field potential, intracellular sharp-electrode as well as whole-cell voltage clamp recording techniques. Intracellular investigations on a broad range of concentrations revealed that the typical neuroleptic haloperidol at higher concentrations significantly depressed the excitatory postsynaptic component induced by electrical stimulation of layer II. This was not seen with the atypical neuroleptics clozapine and iloperidone.

Anticonvulsant properties of the methanolic extract of Cyperus articulatus (Cyperaceae).

The methanolic extract of rhizomes of Cyperus articulatus, a plant used in traditional medicine in Africa and Latin America for many diseases, possesses anticonvulsant activity in mice. This extract protected mice against maximal electroshock (MES)- and pentylenetetrazol (PTZ)-induced seizures. It also delayed the onset of seizures induced by isonicotinic acid hydrazide and strongly antagonized N-methyl-D-aspartate-induced turning behavior.

The potency of the novel tachykinin receptor antagonist CGP49823 at rat and gerbil motoneurones in vitro.

The novel tachykinin receptor antagonist CGP49823 ((2R,4S)-2-benzyl-1-(3,5-dimethylbenzoyl)-4-(quinolin-4-y lmethylamino)piperidine) has been compared with three other selective non-peptide tachykinin NK1 receptor antagonists. The drugs were tested as antagonists of the depolarization of spinal motoneurones induced by bath application of the selective tachykinin NK1 receptor agonist septide-(6-11) (300 nM) for 120 s at 15 min intervals. The antagonists were bath applied and the depolarizations were recorded from lumbar ventral roots of 7 to 12 day old rat and gerbil hemisected spinal cords in vitro.

Comparative in vivo and in vitro studies with the potent GABAB receptor antagonist, CGP 56999A.

CGP 56999A ([3-[1-(R)-[(3-cyclohexylmethyl)hydroxyphosphinyl]-2-(S)- hydroxy-propyl] amino]ethyl]-benzoic acid) is a potent GABAB receptor antagonist showing much more pronounced convulsant features in mice than do other previously studied GABAB receptor antagonists. The goal of this study was to elucidate the physiological mechanisms underlying this effect. In mice a dose of 0.

The effects of neurokinin-1 receptor agonists on spinal motoneurones of the neonatal rat.

The effects of substance P (SP) and the selective NK1 receptor agonist [Sar9Met(O2)11] substance P on neonate rat spinal motoneurones were examined using intracellular recordings. Bath-administration of SP (0.1-3 microM) or [Sar9Met(O2)11] substance P (0.

Phosphinic acid analogues of GABA. 1. New potent and selective GABAB agonists.

The antispastic agent and muscle relaxant baclofen 1 is a potent and selective agonist for bicuculline-insensitive GABAB receptors. For many years efforts to obtain superior GABAB agonists were unsuccessful. We describe the syntheses and biological properties of two new series of GABAB agonists, the best compounds of which are more potent than baclofen in vitro and in vivo.

Physiological and pharmacological characterization of the spinal tachykinin NK2 receptor.

The goal of these investigations was to study the role of tachykinin NK2 receptors in neonatal spinal cords using the selective NK2 receptor agonist [beta-Ala8]neurokinin A-(4-10) and the new NK2 receptor antagonist GR 94800. Experiments were performed with superfused hemisected rat and gerbil spinal cords. Dorsal roots were electrically stimulated and the synaptically elicited responses and the DC-potentials were recorded extracellularly from the corresponding ventral roots.

Contribution of presynaptic GABA-B receptors to paired-pulse depression of GABA-responses in the hippocampus.

The synaptic release of gamma-aminobutyric acid (GABA) is thought to be regulated by presynaptic GABA receptors of the B-type. It was the goal of this study to validate this concept electrophysiologically using four selective antagonists of GABA-B receptors. Experiments were performed in hippocampal slices exposed to 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX 30 microM) and D-2-amino-5-phosphonopentanoate (AP5 40 microM) in order to block excitatory transmission.

Oxcarbazepine: mechanisms of action.

The antiepileptic drug (AED) oxcarbazepine (OCBZ) and its rapidly formed 10-monohydroxy metabolite (MHD) protect against electroshock-induced tonic hindlimb extension in rodents (ED50 14-21 mg/kg p.o.).

Oxcarbazepine: preclinical anticonvulsant profile and putative mechanisms of action.

Oxcarbazepine (OCBZ, Trileptal) and its main human monohydroxy metabolite (MHD) protected mice and rats against generalized tonic-clonic seizures induced by electroshock with ED50 values between 13.5 and 20.5 mg/kg p.

Phenylglycine derivatives antagonize the excitatory response to Purkinje cells to 1S,3R-ACPD: an in vivo and in vitro study.

The interactions of the phenylglycine derivatives (S)-4-carboxyphenylglycine (S-4CPG) and (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) with responses of rat cerebellar Purkinje cells to (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) were examined by intracellular recordings in acute cerebellar slices and extracellular recordings in vivo, using multibarrel electrodes. In vitro, both S-4CPG (100 microM to 1 mM) and MCPG (250 microM to 1 mM) reversibly and dose-dependently reduced an inward current induced by bath-applied 1S,3R-ACPD, an agonist at metabotropic glutamate receptors (mGluRs), in Purkinje cells voltage-clamped at -60 to -65 mV. S-4CPG applied at a concentration of 1 mM reduced the 1S,3R-ACPD induced current to 17% of control values but when applied alone also produced an inward current amounting to 26.

Multiphasic responses of cerebellar Purkinje cells to 1S,3R-ACPD: an in vivo study.

The effects of iontophoretically applied (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), an agonist of metabotropic glutamate receptors, were examined in rat cerebellar Purkinje cells in vivo. Multibarrel electrodes were used for extracellular recordings of spontaneous single unit discharges and iontophoretic ejection of 1S,3R-ACPD. The effect of 1S,3R-ACPD depended on both the strength and the duration of the iontophoretic current.

The modulation of the monosynaptic reflex by substance P in the hemisected spinal cord preparation of the rat and gerbil.

The effects of substance P and the selective neurokinin-1 receptor antagonist (+/-)-CP-96,345 have been compared on in vitro spinal cord preparations from the rat and the gerbil. Substance P produced a concentration-dependent depolarization of motoneurons recorded from ventral roots of both species. The EC50 values (microM mean +/- S.

Stimulation parameters determine role of GABAB receptors in long-term potentiation.

Blockade of GABAB receptors was reported to improve cognitive performance in mammals. The physiological basis of this effect is poorly understood. We investigated the effect of the GABAB receptor antagonist CGP 35348 on long-term potentiation (LTP) in the CA1 area of the hippocampus in vitro and in vivo.