Despite considerable evidence that ethanol can enhance chloride flux through the y-aminobutyric acid type A (GABAA) receptor-channel complex in several central neuron types, the effect ofethanol on hippocampal GABAergic systems is still controversial. Therefore, we have reevaluated this interaction in hippocampal pyramidal neurons subjected to local monosynaptic activation combined with pharmacological isolation of the various components of excitatory and inhibitory synaptic potentials, using intracellular currentand voltage-clamp recording methods in the hippocampal slice. In accord with our previous findings, we found that ethanol had little effect on compound inhibitory postsynaptic potentials/currents (IPSP/Cs) containing both GABAA and GABAB components. However, after selective pharmacological blockade of the GABAB component of the IPSP (GABAB-IPSP/C) by low It is common knowledge that alcohol intoxication and the resulting loss of motor and cognitive control in humans have led to untold trauma and suffering. Despite the likelihood that such problems arise from the action of ethanol on the central nervous system (CNS) and several decades of alcohol research suggesting a general depressant effect of intoxicating doses of ethanol on CNS neurons, until recently little has been known about the mechanisms behind this depression. Studies over the past decade have shown that the most sensitive site for ethanol action is the synapse (1-5), and more recently it has been suggested that ethanol-evoked neuronal depression might arise from either a blunting of excitatory glutamatergic synaptic transmission (see, e.g., refs. 6-8) and/or an enhancement of inhibitory y-aminobutyric acid (GABA)ergic transmission (see refs. 4 and 9).With regard to inhibitory neurotransmission, ethanol has often been reported to enhance GABAA receptor activation, and the resulting Cl-currents or fluxes, in neurons or isolated preparations of several brain regions (4,9 (see refs. 24-26). In addition, the development of local or focal stimulation techniques (27,28), combined with these selective antagonists, now allows study of pharmacologically isolated synaptic components. Therefore, we have repeated earlier studies of ethanol effects on GABAergic monosynaptic IPSPs with two different slice preparation methods, including the one used in previous studies from our laboratory (13), but now with pharmacologically isolated IPSP components. We now report that, under these conditions, low ethanol concentrations reproducibly enhance GABAAergic IPSPs of hippocampal pyramidal neurons (HPNs), but only when GABAB receptors are blocked.MATERIALS AND METHODS Preparation. The two hippocampal slice preparations used were as described (13,29,30). In brief, male Sprague-Dawley Abbreviations: IPSP/C, inhibitory postsynaptic potential/current; IPSC, inhibitory postsynaptic current; HPN, hippocampal pyramidal neuron; GABA, y-aminobutyric acid; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; d-APV, DL-2-amino-5-phosphonovaleric acid; ACSF, artificial cer...

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Prepulse inhibition (PPI) of the startle reflex is reduced by systemic administration of dopamine (DA) agonists. Since PPI is impaired in patients with schizophrenia, the DA agonist-induced disruption of PPI in rats may be a useful model for studying the pathophysiology of impaired sensorimotor gating in schizophrenia. In the present study, we replicated the observation that PPI is disrupted by systemic administration of the D2 agonist quinpirole, but not by the D1 agonist SKF 38393. PPI caused by weak [1-5 dB(A)] or more intense [10 dB(A)] prepulses was also disrupted by quinpirole infusion into the nucleus accumbens (NAC). The effects of intraaccumbens quinpirole on PPI were blocked by pretreatment with the D2 antagonist haloperidol. These results support the notion that the reduction of PPI after systemic administration of DA agonists is mediated via stimulation of NAC D2 receptors.

Abstract-There is increasing recognition that communication pathways exist between the immune system and brain, which allows bidirectional regulation of immune and brain responses to infection. The endotoxin lipopolysaccharide (LPS) has been reported to elicit release of cytokines and expression of inducible nitric oxide synthase (iNOS) in peripheral organs. Whereas LPS given systemically causes endotoxic shock, little is known about its central nervous system action, particularly the induction of iNOS. Nitric oxide (NO) and glutamate in the nucleus tractus solitarii (NTS) are important mediators of central cardiovascular regulation. We have previously demonstrated that intravenous injections of LPS increased the NO precursor L-arginine-induced depressor effect in the NTS. The present study investigated further the effects of LPS on the release of NO and glutamate in the NTS and the expression of c-fos, an immediate early response gene product, in neural substrates for central cardiovascular control. In vivo microdialysis coupled with chemiluminescence and electrochemical detection techniques were used to measure extracellular levels of NO and glutamate in the rat NTS. Immunohistochemistry was used for the examination of c-fos protein expression. We found that intravenous infusion of LPS (10 mg/kg) produced a biphasic depressor effect, with an early, sharp hypotension that partially recovered in 15 minutes and a secondary, more prolonged hypotension. In the NTS, a progressive increase of extracellular glutamate and NO levels occurred 3 and 4 hours after LPS was given, respectively. The effects of LPS on the induction of delayed hypotension and NO formation in the NTS were abolished by pretreatment with the iNOS inhibitor aminoguanidine. Finally, c-fos protein expression in the NTS and related structures for cardiovascular regulation was observed after LPS challenge. Taken together, these data suggest that an endotoxin given systemically can elicit delayed increases of glutamate release and iNOS-dependent NO production in the NTS and activate the central neural pathway for modulating cardiovascular function. (Hypertension. 1999;33:1218-1224.)Key Words: nitric oxide synthase Ⅲ endotoxin Ⅲ cardiovascular system Ⅲ microdialysis N itric oxide (NO), a free-radical gas produced from L-arginine by the enzyme NO synthase (NOS), is a remarkable regulatory molecule that plays an important role in a variety of physiological functions. Several isoforms of NOS have been isolated and purified. The NOS in endothelial (eNOS) and neuronal (nNOS) cells are expressed constitutively, and their activities are regulated by changes in intracellular calcium. In contrast, activation of macrophages with endotoxins and/or cytokines results in the de novo biosynthesis of a calcium-independent (inducible) isoform of NOS (iNOS). 1 The iNOS-mediated NO formation induced by endotoxins is responsible for the fall of blood pressure in endotoxic shock. 2 The endotoxin lipopolysaccharide (LPS) is a unique glucosamine-based phospholipid that makes u...

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