SUMMARY1. Neostriatal neurones were recorded intracellularly from a rat corticostriatal slice preparation. Depolarizing postsynaptic potentials (DPSPs) were evoked by either cortical or intrastriatal stimulation.2. Kynurenic acid (600 /tM), an antagonist of excitatory amino acids, reduced the cortically-evoked DPSPs by 88 % while the intrastriatally evoked potentials were reduced by 48 %. Bicuculline (100,tM) produced only a slight inhibition of the cortically evoked DPSPs (12 %), but clearly depressed intrastriatal potentials (52 %).3. The effects of (-)-baclofen, a y-aminobutyric acid (GABA)B receptor agonist, were studied on the cortically evoked DPSPs. In all the tested neurones (-)-baclofen, added to the superfusion medium, caused a concentration-dependent decrease of these potentials (half-maximal effect (EC50) = 800 nM). This effect was not affected by bicuculline. (-)-Baclofen did not change the membrane potential, the input resistance, current-evoked firing frequency, or postsynaptic responses to exogenously applied glutamate.4. The effects of (-)-baclofen on the DPSPs were compared to those produced by application of GABA and muscimol. GABA and muscimol decreased the DPSPs and caused a membrane depolarization coupled with a decrease of the membrane resistance. Bicuculline (100 JtM) blocked the GABA-induced changes of the membrane potential and of the resistance, but not the decrease of the synaptic potentials. All the effects produced by muscimol were blocked by bicuculline.5. Following intrastriatal stimulation a residual kynurenate-insensitive potential persisted; this potential was blocked by bicuculline (100 ,tM). (-)-Baclofen produced a dose-dependent decrease of this potential (EC50 = 800 nM). The postsynaptic responses to exogenously applied GABA were unchanged by (-)-baclofen.6. The amplitude of kynurenate and bicuculline-sensitive DPSPs were stable at a frequency of 0 1 Hz. At frequencies between 0 3 and 3 Hz both these potentials were attenuated with the second stimulus and after about five stimuli a steady state was reached. Membrane potential and input resistance were not affected by these frequencies of stimulation.* To whom correspondence should be addressed. MS 8751P. CALABRESI AND OTHERS 7. Application of the GABA uptake inhibitor nipecotic acid (100-300 1uM) clearly reduced the amplitude of both kynurenate-and bicuculline-sensitive DPSPs evoked at low frequencies of stimulation (0-01-0{3 Hz), but had lower effects at higher stimulation rates (1-3 Hz). Application of nipecotic acid increased the duration of membrane responses to exogenously applied GABA.8. Applications of either 2-hydroxy-saclofen (100 JM) or phaclofen (0-7-1 mm), antagonists of the GABAB receptors, produced a parallel shift to the right of the dose-response curve of the effect of (-)-baclofen on the bicuculline-sensitive DPSPs, but did not significantly antagonize the effect of this agonist on the kynurenatesensitive DPSPs. 2-Hydroxy-saclofen produced an increase in the amplitude of bicuculline-sensitive DPSPs, while i...

The excess of psychiatric comorbidity in patients with MOH can be related either to medication overuse or to chronification of headache. Among anxiety disorders, we observed a high rate of subclinical OCD. However, a direct link between compulsive behavior and medication overuse cannot be established yet. OCD in MOH might be underdiagnosed and undertreated.

In Huntington's disease neuronal degeneration mainly involves medium-sized spiny neurons. It has been postulated that both excitotoxic mechanisms and energy metabolism failure are implicated in the neuronal degeneration observed in Huntington's disease. In central neurons, > 40% of the energy released by respiration is used by Na+/K+ ATPase to maintain ionic gradients. Considering that impairment of Na+/K+ ATPase activity might alter postsynaptic responsivity to excitatory amino acids (EAAs), we investigated the effects of the Na+/K+ ATPase inhibitors, ouabain and strophanthidin, on the responses to different agonists of EAA receptors in identified medium-sized spiny neurons electrophysiologically recorded in the current- and voltage-clamp modes. In most of the cells both ouabain and strophanthidin (1-3 microM) did not cause significant change in the membrane properties of the recorded neurons. Higher doses of either ouabain (30 microM) or strophanthidin (30 microM) induced, per se, an irreversible inward current coupled to an increase in conductance, leading to cell deterioration. Moreover, both ouabain (1-10 microM) and strophanthidin (1-10 microM) dramatically increased the membrane depolarization and the inward current produced by subcritical concentrations of glutamate, AMPA and NMDA. These concentrations of Na+/K+ ATPase inhibitors also increased the membrane responses induced by repetitive cortical activation. In addition, since it had previously been proposed that dopamine mimics the effects of Na+/K+ ATPase inhibitors and that dopamine agonists differentially regulate the postsynaptic responses to EAAs, we tested the possible modulation of EAA-induced membrane depolarization and inward current by dopamine agonists. Neither dopamine nor selective dopamine agonists or antagonists affected the postsynaptic responses to EAAs. Our experiments show that impairment of the activity of Na+/K+ ATPase may render striatal neurons more sensitive to the action of glutamate, lowering the threshold for the excitotoxic events. Our data support neither the role of dopamine as an ouabain-like agent nor the differential modulatory action of dopamine receptors on the EAA-induced responses in the striatum.