Objective. Multimodal measurements at the neuronal level allow for detailed insight into local circuit function. However, most behavioral studies focus on one or two modalities and are generally limited by the available technology. Approach. Here, we show a combined approach of electrophysiology recordings, chemical sensing, and histological localization of the electrode tips within tissue. The key enabling technology is the underlying use of carbon fiber electrodes, which are small, electrically conductive, and sensitive to dopamine. The carbon fibers were functionalized by coating with Parylene C, a thin insulator with a high dielectric constant, coupled with selective re-exposure of the carbon surface using laser ablation. Main results. We demonstrate the use of this technology by implanting 16 channel arrays in the rat nucleus accumbens. Chronic electrophysiology and dopamine signals were detected 1 month post implant. Additionally, electrodes were left in the tissue, sliced in place during histology, and showed minimal tissue damage. Significance. Our results validate our new technology and methods, which will enable a more comprehensive circuit level understanding of the brain.

The sensory properties of a reward-paired cue (a conditioned stimulus; CS) may impact the motivational value attributed to the cue, and in turn influence the form of the conditioned response (CR) that develops. A cue with multiple sensory qualities, such as a moving lever-CS, may activate numerous neural pathways that process auditory and visual information, resulting in CRs that vary both within and between individuals. For example, CRs include approach to the lever-CS itself (rats that "sign-track"; ST), approach to the location of reward delivery (rats that "goal-track"; GT), or an "intermediate" combination of these behaviors. We found that the multimodal sensory features of the lever-CS were important to the development and expression of sign-tracking. When the lever-CS was covered, and thus could only be heard moving, STs not only continued to approach the lever location but also started to approach the food cup during the CS period. While still predictive of reward, the auditory component of the lever-CS was a much weaker conditioned reinforcer than the visible lever-CS. This plasticity in behavioral responding observed in STs closely resembled behaviors normally seen in rats classified as "intermediates." Furthermore, the ability of both the lever-CS and the reward-delivery to evoke dopamine release in the nucleus accumbens was also altered by covering the lever-dopamine signaling in STs resembled neurotransmission observed in rats that normally only GT. These data suggest that while the visible lever-CS was attractive, wanted, and had incentive value for STs, when presented in isolation, the auditory component of the cue was simply predictive of reward, lacking incentive salience. Therefore, the specific sensory features of cues may differentially contribute to responding and ensure behavioral flexibility.

The GABA derivative TZ-50-2 exerted pronounced antiarrhythmic effects on a variety of arrhythmias (atrial, ventricular, and mixed). The drug was superior (or at least comparable) to quinidine, procainamide, lidocaine, verapamil, bonnecor, and other reference drugs in antiarrhythmic activity and therapeutic range, and showed no cardiotoxicity. The antiarrhythmic effects of TZ-50-2 were due to modulation of calcium and sodium channels. Key Words: GABA; cardiac arrhythmiasAntiarrhythmic potency of local anesthetics and anticonvulsants with similar mechanisms of action attracts now considerable attention [10]. The novel GABA derivative hemisuccinate 4-oxi-3-benzylamino-N-benzylbutan amide (laboratory code TZ-50-2) exhibits both local anesthetic [9] and anticonvulsant properties [6]. This work was aimed at investigation of antiarrhythmic activity (AA) of TZ-50-2 on different models of atrial, ventricular, and mixed arrhythmias. MATERIALS AND METHODSExperiments were carried out on 446 outbred male albino rats (175-220 g), 48 mongrel rabbits (2.8-3.6 kg), 98 cats (2.6-4.2 kg), and 31 dogs (14-22 kg) of both sexes, as well as on isolated atria (trabecular and auricular preparations) of frogs (n=36) and guinea pigs (n=20).Toxicity of TZ-50-2 and reference drugs (mean lethal dose, LDs0 ) was determined in experiments on rats with single intravenous injection followed by 48-h monitoring [3,7].The ECG (R, RR, QT, PQ, QRS) were recorded in standard lead II with EKIT-04 electrocardiograph in experiments on dogs under pentobarbital anesthesia (40 mg/kg, intrapleurally) with drug administration by biological titration (1 mg/kg/ml) until cardiac arrest. Drug effects on the myocardial reli;actory period were studied on isolated auricles of guinea pig heart [8]. The effects on action potentials and transmembrane ionic currents were studied on isolated atrial trabeculas from the heart of Rana ridibunda [ 12].The antiarrhythmic efficacy of the drugs was evaluated by comparing their potencies (mean effective doses, EDs0) and antiarrhythmic indices (LDs0/ED~0) characterizing the therapeutic window (TW) [3].The data were analyzed statistically [3]. RESULTSIntravenous inl~asion of TZ-50-2 had no effect on the ECG indices in the anesthetized dogs up to a total dose of 50 mg/kg (reached over 50 min). Further infusion (up to 60-120 mg/kg) caused respiration arrest

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Intravenous injection of T3-146, a cyclic derivative of,/-aminobutyric acid (structural analog of piracetam), 5 min prior to reperfusion of the descendent branch of the left coronary artery prevents the development of serious rhythm disturbances and stabilizes hemodynamics and cardiac function. These effects are probably due to the inhibitory effect of this compound on lipid peroxidation in the myocardium. Key Words: ~[-aminobutyric acid; ischemia; reperfusion; disturbances of cardiac rhythm and hemodynamic; treatmentReperfusion of coronary vessels is the most effective approach to correcting myocardial ischemia [11]. However, this procedure can aggravate damage to the myocardium and cause the reperfusion syndrome characterized by high risk of cardiac rhythm disturbances (CRD), including ventricular fibrillation [1,4,12].Previous studies have demonstrated that drugs stimulating central and peripheral GABAergic stresslimiting systems possess antiarrhythmic and antifibrillatory activity under conditions of acute regional myocardial ischemia and reperfusion [5,7]. In light of this, it seems interesting to study antiarrhythmic and antifibrillatory effects of a new cyclic derivative of ~/-aminobutyric acid (laboratory code T3-146) under conditions of reperfusion in cats. This agent is a structural analog of piracetam and possesses cardioprotective properties. MATERIALS AND METHODSExperiments were carried out on 96 albino male rats (0.155-0.210 kg) and 60 nonpedigree cats (2.6-3.5Department of Pharmacology, Kuban Medical Academy, Krasnodar kg). Acute toxicity (mean lethal dose, LDs0 ) of the T3-146 and reference preparations was determined in rats as described previously [6].Reperfusion CRD were modeled on cats narcotized with Nembutal (40 rng/kg, intraperitoneally) and artificially ventilated [3]. After thoracotomy, the descendent branch of the left coronary artery was occluded near the lower edge of the auricle for 30 rain. Removal of the ligature induced reperfusion ventricular arrhythmias which in most cases transformed into ventricular fibrillation. T3-146 and reference preparations were injected intravenously slowly in isotoxic doses (5% LDs0 ) 5 min prior to coronary occlusion. The occurrence of repeffusion ventricular arrhythmias and fibrillation was recorded on an EKIT-04 electrocardiograph.The effect of T3-146 on the main hemodynamic and cardiac parameters (HCP) was studied on cats narcotized with Nembutal (40 mg/kg, intraperitoneally) and artificially ventilated as described previously [9]. Systemic arterial and left ventricular pressures as well as its first and second derivatives (dP/dt and (dP/dt)/P) characterizing myocardial contractility were recorded. Electrocardiogram in