The frequency of rat's hippocampal theta rhythm is related to the speed of locomotion

Hippocampal EEG activity was recorded in rats during locomotion, spontaneous or induced by electrical stimulation of subthalamic locomotor region (SLR) and posterior hypothalamus (PH). Spontaneous locomotion was associated with the theta frequency (6–8.5 Hz). Electrically induced locomotion was also associated with theta rhythm, frequency of which depended on the site of stimulation. Theta frequency during SLR evoked locomotion was almost the same as during spontaneous locomotion (7–9 Hz). PH induced locomotion was accompanied by higher theta frequency (9–11 Hz). Theta frequency and the speed of locomotion were positively correlated during spontaneous locomotion. During electrically induced locomotion the theta frequency was much higher than expected when related to the speed of spontaneous locomotion. The electrically evoked locomotion may result from activation of various systems. Stimulation of the SLR activates system responsible for the exploratory behavior, while stimulation of PH evokes locomotion related to aversive behavior. Thus, we conclude that the theta rhythm frequency may depend not only on the speed of locomotion but also on the rats' motivational–emotional state, associated with locomotion performed by the animal.     

Hippocampal mobility-related theta activity is not diminished by vigabatrin, a GABAmimetic antiepileptic drug, in normal rats.

Lesions causing loss of hippocampal theta activity have been shown to result in spatial memory deficits in rats. On the other hand, hippocampal theta activity is thought to be associated only with motor activity, and its role in learning/memory is not clear. Vigabatrin, an inhibitor of GABA-tranasminase, causes elevation of brain GABA levels. Previously, we have found that subchronic administration of vigabatrin did not impair spatial learning/memory in a water maze task. This experiment was carried out to further examine the hippocampal effects of vigabatrin by studying whether vigabatrin at antiepileptic doses affects mobility-related hippocampal EEG. Administration of vigabatrin (100 mg/kg or 500 mg/kg, IP) to nonepileptic rats caused no significant changes in mobility-related rhythmic theta activity, and the relative spectral power of theta frequency had a slight increasing tendency. These results suggest that the vigabatrin-induced enhanced GABAergic inhibition does not disturb normal mobility-related hippocampal theta activity.     

The effects of vigabatrin on spike and wave discharges in WAG/Rij rats

The effects of vigabatrin, which increases GABA concentrations by inhibiting GABA transaminase, on spike and wave discharges (SWDs) in the electroencephalogram of WAG/Rij rats were studied. Vigabatrin increased the incidence and duration of the SWDs, suggesting a quantitative GABA(A)ergic involvement in the mechanism(s) underlying the starting and stopping of an ongoing SWD. Also, vigabatrin decreased the SWD peak frequency, suggesting an important role of GABA(B) in the mechanism(s) underlying the peak frequency of the SWDs. Vigabatrin gradually changed the course of the hazard rates of the SWD durations, suggesting a qualitative GABAergic role in the mechanism(s) underlying the stopping of an ongoing SWD.     

Hippocampal theta activity related to elicitation and inhibition of approach locomotion

This study determined if the hippocampal theta rhythm showed phase relationships or changes in amplitude and frequency with the onset of stimuli and locomotion in a task in which auditory cues initiated and suppressed approach locomotion. Rats with electrodes in the dorsal hippocampus lapped at a milk dipper and were presented a tone which predicted the delivery of a food pellet. In some trials the pellet cue tone was negated by 60-Hz clicks beginning 0.3 s after onset, and no pellet was delivered. A video capture system (20-ms sampling) synchronized to the hippocampal recording system (10-ms sampling) was used to determine the onset of locomotor approach to the pellet area. The findings failed to support proposals that phase-related mechanisms play a role in encoding and retrieval of movement-related information. Neither the pellet cue nor the negating cue reset the theta rhythm, and they did not produce differential evoked potentials. During milk lapping, theta amplitude increased in the 1/2 s prior to all pellet cues regardless of their locomotor effect. Frequency also rose but only when a non-negated pellet elicited short-latency locomotion. During locomotor execution, theta peak amplitude peaked earlier than theta frequency by approximately one period. In general during performance of this task, increasing theta amplitude reflected a general preparation to process the cue and increasing theta frequency reflected the readiness to respond to the cue with locomotion.     

Vigabatrin extracellular pharmacokinetics and concurrent γ-aminobutyric acid neurotransmitter effects in rat frontal cortex and hippocampus using microdialysis

Purpose:   To investigate the pharmacokinetic interrelationship of vigabatrin in blood and the brain (frontal cortex vs. hippocampus) and to ascertain the relationship between brain extracellular vigabatrin concentrations and concurrent γ-aminobutyric acid (GABA) concentrations.
Methods:   Sprague-Dawley rats were implanted with a jugular vein catheter for blood sampling, and microdialysis probes in the frontal cortex and hippocampus for extracellular fluid (ECF) sampling. Vigabatrin was administered intraperitoneally at two different doses (500 and 1,000 mg/kg), and blood and ECF were collected at timed intervals up to 8 h. Rats were freely moving and behaving. Vigabatrin (sera and ECF) and GABA (ECF) concentrations were measured with use of high performance liquid chromatography (HPLC).
Results:   Vigabatrin concentrations in blood rose linearly and dose-dependently, and vigabatrin rapidly appeared in the brain as evidenced by the detection of vigabatrin in the ECF of both the frontal cortex and hippocampus at time of first sampling (15 min). However, frontal cortex concentrations were twofold greater than those of the hippocampus. Furthermore, GABA concentrations increased five-fold in the frontal cortex but were unaffected in the hippocampus. In addition, GABA concentrations began to increase approximately 3 h after vigabatrin administration at a time when vigabatrin concentrations were in exponential decline.
Conclusions:   Vigabatrin distribution in the brain is region specific, with frontal cortex concentrations substantially greater than those seen in the hippocampus. Elevation of GABA concentrations did not reflect the concentration profile of vigabatrin but reflected its regional distribution.     

Walking performance of vestibular-defective patients before and after unilateral vestibular neurotomy

The present study investigated goal-directed linear locomotion in nine Menière’s patients before and after (1 week, 1 and 3 months) a curative unilateral vestibular neurotomy (UVN). Experiments were done using a 3D motion analysis system in subjects walking eyes open (EO) and eyes closed (EC) towards a real or memorized target, respectively. Locomotor pattern (velocity, step length, step frequency and walk ratio) and walking trajectory deviations were evaluated for normal and fast speeds of locomotion and compared to those recorded in 10 healthy subjects. Before UVN, patients showed no walking deviation but gait pattern changes characterized by slower walks compared to the controls, mainly due to step length and step frequency reductions for both visual conditions and locomotion speeds. In the acute stage after UVN, locomotor pattern impairments were significantly accentuated. On the other hand, patients showed strong walking deviations towards the lesioned side with EC. Opposite lateral deviation towards the intact side were observed with EO for normal speed only. Recovery from impaired locomotor pattern was achieved within 1 month for normal speed but remained uncompensated 3 months post-lesion for fast speed particularly in EC condition. Finally, the walking trajectory deviation towards the lesioned side in the dark was maintained up to 3 months after UVN. The results show that central processing of visual and vestibular cues contributes to an accurate locomotor pointing. They argue for an increased weight of visual reference frame on locomotor functions when vestibular function is unilaterally impaired.     

Hippocampal theta activity and behavioral sequences in a reward-directed approach locomotor task

Hippocampal rhythmic slow wave activity (theta) has been implicated in the processing of stimuli associated with movement. This study determined whether the theta rhythm showed phase relationships or changes in amplitude and frequency with the onset of stimuli and behavioral sequences in a skilled locomotor approach task. Rats with bipolar electrodes spanning CA1 approached a stall, turned to enter it, approached and depressed a treadle, waited 1.35 s, and approached a milk reward located forward either to the right or to the left. Auditory cues indicated the location of the reward during the waiting period and at the reward onset. A video capture system (20-ms sampling) was synchronized to the hippocampal recording system (10-ms sampling). Behavioral events identified by motion analysis were used to generate averages of hippocampal slow wave activity, theta peak amplitudes, and intervals between peaks. Theta activity at 8-10 Hz was almost continuous during the behavioral sequences. Phase relations with stimuli or movement onsets occurred infrequently and were not consistent across the four subjects. Theta peak amplitude and frequency decreased as the rat slowed locomotion in the stall and reached the treadle. Onset of locomotion directed to a reward location occurred on a positive peak of averaged theta activity. When locomotion had short latencies, increases in theta frequency appeared after the onset but, when it had longer latencies, frequency increases appeared 200 ms before onset. The results indicate that the execution of instrumental movement modulates both theta amplitude and frequency, and that the preparation for locomotion modulates theta frequency.     

Factors that determine the magnitude and time course of human H-reflexes in locomotion

The soleus H-reflex amplitude is deeply modulated during locomotion in humans (Capaday and Stein, 1986). Moreover, at a constant stimulus intensity, the slope of the relationship between the amplitude of the soleus H-reflex and the background electromyogram (EMG) changes with different locomotor tasks (Capaday and Stein, 1987a). Two further aspects are studied here. First, we recorded the reflex during overlapping speeds of walking (2.0-7.5 km/hr) and running (5-9 km/hr) to determine whether the speed, the motor output, or the form of locomotion was most important in setting the slope of this relationship between H-reflex and background EMG. Second, we determined the time course of change in the H-reflex amplitude and the possible site of action for the reflex depression during the transition from standing to walking. The primary determinant of the slope was found to be the form of locomotion. The differences between running and walking could not be explained entirely by either movement speed or motor output. For walking, the slope varied inversely with the speed and the motor output of locomotion. This compensation in slope as a function of motor output may prevent saturation of the motoneuron pool. The appropriate reflex amplitudes for a particular locomotor pattern are activated rapidly and completely within a reaction time, and simultaneously with the activation of muscle activity for the initiation of walking. Mechanisms for the rapid change seen during the initiation of locomotion most likely act presynaptically on the muscle spindle afferents. The time course and magnitude of this change are correlated with the activity of the tibialis anterior muscle.     

Speed modulation of hippocampal theta frequency correlates with spatial memory performance

Hippocampal theta rhythm is believed to play a critical role in learning and memory. In animal models of temporal lobe epilepsy (TLE), there is evidence that alterations of hippocampal theta oscillations are involved in the cognitive impairments observed in this model. However, hippocampal theta frequency and amplitude at both the local field potential (LFP) and single unit level are strongly modulated by running speed, suggesting that the integration of locomotor information into memory processes may also be critical for hippocampal processing. Here, we investigate whether hippocampal speed‐theta integration influences spatial memory and whether it could account for the memory deficits observed in TLE rats. LFPs were recorded in both Control (CTR) and TLE rats as they were trained in a spatial alternation task. TLE rats required more training sessions to perform the task at CTR levels. Both theta frequency and power were significantly lower in the TLE group. In addition, speed/theta frequency correlation coefficients and regression slopes varied from session to session and were worse in TLE. Importantly, there was a strong relationship between speed/theta frequency parameters and performance. Our analyses reveal that speed/theta frequency correlation with performance cannot merely be explained by the direct influence of speed on behavior. Therefore, variations in the coordination of theta frequency with speed may participate in learning and memory processes. Impairments of this function could explain at least partially memory deficits in epilepsy. © 2013 Wiley Periodicals, Inc.     

Effect of Vigabatrin on the Electroencephalogram in Rats

Vigabatrin (gamma-vinyl GABA; GVG) is a new antiepileptic drug (AED) that increases the level of the inhibitory transmitter, gamma-aminobutyric acid (GABA) in the brain. We evaluated the effect of GVG on the EEG of normal rats. GVG was administered intraperitoneally (i.p.) at a dose of 100 mg/kg once a day for 12 days. EEG was recorded at baseline, on the fourth day, at the end of the 12-day GVG period and 10 days after discontinuation of GVG. GVG increased the amplitude of delta (1-4 Hz) and theta (4-8 Hz) frequency bands and resulted in slowing of the peak frequency (Fp) and mean frequency (Fm) in both the frontal and occipital cortex, especially during waking-immobility. EEG changes normalized within 10 days after the last GVG injections. The results suggest that a relationship may exist between the EEG changes and increase in GABA levels with GVG.     

The pharmacokinetics of vigabatrin in rat blood and cerebrospinal fluid.

PURPOSE: Data on the blood pharmacokinetics of vigabatrin, an antiepileptic drug with a unique and novel mechanism of action, in the rat are sparse. Additionally, little is known of the kinetics of vigabatrin in the central cerebrospinal fluid (CSF) compartment. We therefore investigated the rate of penetration into and the inter-relationship between serum and CSF compartments following systemic administration of vigabatrin in the rat. METHODS: Sprague-Dawley rats were implanted with a jugular vein catheter and a cisterna magna catheter for blood and CSF sampling, respectively. Vigabatrin was administered by intraperitonial injection at three different doses (250, 500 and 1000mg/kg) and blood and CSF collected at timed intervals up to 8h. Vigabatrin concentrations in sera and CSF were determined by high performance liquid chromatography. RESULTS: Vigabatrin concentrations in blood and CSF rose linearly and dose-dependently and the time to maximum concentration (Tmax) was 0.4 and 1.0h, respectively. Vigabatrin is not protein bound in serum and its elimination from serum (mean t1/2 values, 1.1-1.4 h) is rapid and dose-independent. The efflux of vigabatrin from CSF was significantly slower than that seen for serum (mean t1/2 values, 2.2-3.3h). CONCLUSIONS: The kinetics of vigabatrin are linear with rapid entry into CSF. However, although vigabatrin CSF kinetics parallel that seen in serum, CSF vigabatrin concentrations represent only 2% of concentrations seen in serum and do not reflect free drug concentrations in serum.     

Increase in hippocampal theta oscillations during spatial decision making

The processing of spatial and mnemonic information is believed to depend on hippocampal theta oscillations (5–12 Hz). However, in rats both the power and the frequency of the theta rhythm are modulated by locomotor activity, which is a major confounding factor when estimating its cognitive correlates. Previous studies have suggested that hippocampal theta oscillations support decision‐making processes. In this study, we investigated to what extent spatial decision making modulates hippocampal theta oscillations when controlling for variations in locomotion speed. We recorded local field potentials from the CA1 region of rats while animals had to choose one arm to enter for reward (goal) in a four‐arm radial maze. We observed prominent theta oscillations during the decision‐making period of the task, which occurred in the center of the maze before animals deliberately ran through an arm toward goal location. In speed‐controlled analyses, theta power and frequency were higher during the decision period when compared to either an intertrial delay period (also at the maze center), or to the period of running toward goal location. In addition, theta activity was higher during decision periods preceding correct choices than during decision periods preceding incorrect choices. Altogether, our data support a cognitive function for the hippocampal theta rhythm in spatial decision making. © 2014 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

Effects of corticotropin-releasing factor (CRF) and opiates on amphibian locomotion

Male rough-skinned newts (Taricha granulosa) were used as a model for the study of the neuroendocrine regulation of locomotion. Intracerebroventricular (i.c.v.) injections of nanogram quantities of corticotropin-releasing factor (CRF) dose-dependently increased locomotion as measured in a circular open-field test arena. In other studies animals received intraperitoneal (i.p.) injections of saline or naloxone, a synthetic opioid antagonist, followed by i.c.v. injections of saline or CRF. With 1-min intervals between injections, neither i.p. saline nor naloxone injections modified the stimulatory effects of CRF injections on locomotor activity. In contrast, with 20-min intervals between injections, the naloxone-plus-CRF injected newts displayed more locomotor activity than the saline-plus-CRF injected newts, suggesting that the opioid system modulated the behavioral effects of CRF. An i.p. injection of bremazocine, an opiate kappa-receptor agonist, suppressed spontaneous locomotion but not CRF-induced locomotion. In contrast, an i.p. injection of morphine, an opiate mu-receptor agonist, did not affect spontaneous locomotion but reduced CRF-induced locomotion, indicating further that the opioid system may modulate the behavioral effects of CRF in this amphibian. The present study provides the first evidence that both CRF and opioids may be involved in the regulation of amphibian locomotor activity.     

Dose and behavioral context dependent inhibition of movement and basal ganglia neural activity by Delta-9-tetrahydrocannabinol during spontaneous and treadmill locomotion tasks in rats

The effects of Delta-9-tetrahydrocannabinole (Delta-9-THC) on locomotor activities and related basal ganglia neural responses were investigated in rats. A multiple-channel, single unit recording method was used to record neuronal activity in the dorsal lateral striatum, the globus pallidus, the subthalamic nucleus, and the substantia nigra pars reticulata simultaneously during spontaneous movement and treadmill locomotion. Delta-9-THC treatment (0.05-2.0 mg/kg, i.p.) dose-dependently decreased spontaneous motor activity and altered walking patterns in treadmill locomotion in that stance time was increased and step number was decreased. In parallel with the behavioral effects, Delta-9-THC treatment inhibited neural activity across all four basal ganglia areas recorded during both motor tests. Further, this inhibition of basal ganglia neural activity was behavioral context-dependent. Greater inhibition was found during resting than during walking periods in the treadmill locomotion test. Delta-9-THC treatment also changed firing patterns in the striatum and globus pallidus. More neurons in these regions discharged in an oscillatory pattern during treadmill walking with Delta-9-THC, and the oscillatory frequency was similar to that of the step cycle. Synchronized firing patterns were found in few basal ganglia neurons in the control condition (approximately 1%). Synchronized firing patterns increased during the treadmill resting phase after Delta-9-THC treatment, but still represented a very small proportion of the total neural population (1.9%). The drug treatment did not change neural responses to the tone cue proceeding treadmill locomotion. This study demonstrates dose-dependent inhibitory effects of cannabinoid injection on motor activity. This effect may be related to the behavioral context-dependent inhibition observed in the basal ganglia system where CB1 receptors are densely distributed.     

Non-vision adverse events with vigabatrin therapy

Vigabatrin is an effective antiepileptic drug (AED) for the treatment of refractory complex partial seizures (rCPS) and infantile spasms (IS). In clinical trials, vigabatrin was generally well-tolerated with an adverse event profile similar to that of other AEDs. The most common treatment-related adverse events were central nervous system effects, including drowsiness, dizziness, headache, and fatigue, with adjunctive vigabatrin in adults with rCPS, and sedation, somnolence, and irritability with vigabatrin monotherapy in infants with IS. Vigabatrin had little effect on cognitive function, mood, or behavior in a battery of neuropsychologic tests for rCPS. In placebo-controlled clinical trials, the incidence of depression and psychosis, but not other psychiatric adverse events, was greater with vigabatrin than placebo. Intramyelinic edema (IME) was initially identified in rats and dogs and led to a temporary suspension of clinical trials in the United States. IME was subsequently correlated with delays in evoked potential (EP) and increased T(2) -weighted signals on magnetic resonance imaging (MRI). Clinical trials of vigabatrin were allowed to resume after IME was not detected by neuropathologic assessments of autopsy and neurosurgical specimens or by serial EP or MRI assessments in older children and adults receiving vigabatrin. Subsequently, MRI abnormalities characterized by increased T(2) intensity and restricted diffusion were identified in infants treated with vigabatrin for IS. These abnormalities generally resolved with discontinuation of vigabatrin and, in some cases, during continued therapy. The benefit of improved seizure control must be balanced against the potential risks associated with vigabatrin, including abnormal MRI changes and other vigabatrin-related safety issues.     

Hippocampal theta activity and facilitated locomotor stepping produced by GABA injections in the midbrain raphe region

Inactivation of neurons in the midbrain raphe region produces increases in locomotor activity, and it appears that they function to suppress locomotion. Inactivation of neurons there also produces hippocampal slow wave (theta) activity and it appears that they also function to inhibit rhythmic activity in the hippocampus. We determined whether the degree of association between the two effects was consistent with the operation of a single mechanism. Stimulation electrodes were implanted into locomotor sites of the hypothalamus of 34 urethane-anesthetized rats. Hindlimb stepping was elicited by 5.12-s trains of perifornical electrical stimulation presented once per minute. Hippocampal theta activity was recorded across the CA1 layer of the dorsal hippocampus. GABA injections were used to locate raphe sites at which neuronal inactivation influenced stepping and hippocampal activity. A glass pipette (80-microm tip) was inserted into the midbrain, and injections of GABA (50-100 mg/0.1-0.2 microl) were made in 70 sites in the midbrain. Injections at 34 sites facilitated stimulation-elicited stepping, and at 17 sites, they also produced intertrial stepping. Facilitating injections, but not ineffective or suppressive injections, increased the mean peak frequency of hippocampal activity, and increased power in the 4-5 Hz band during the period that preceded the stimulation trains, but did not change the 5-6 Hz activity produced during the stimulation trains. Priming locomotor stimulation which also facilitated stepping produced generally similar increases in pre-stimulation peak frequency and 4-Hz power. The magnitudes of the increases in stepping and 4-Hz power were uncorrelated. The increase in 4-Hz power appeared earlier than the increase in stepping in 18 of 34 cases, and later in 11 cases; no increases in 4-Hz power were apparent in five cases. The results indicate that pre-locomotor 4-Hz hippocampal activity in the urethane-anesthetized rat is loosely coupled with facilitated locomotor initiation. Neurons in the midbrain raphe region appear to suppress both processes, but the low degree of association between the magnitudes and onset times of increases in stepping and hippocampal 4-Hz power indicate the operation of multiple mechanisms.     

Kinematic analysis of the different types of locomotor movement in rats after deafferentation

Comparative analysis of kinematics of rat hindlimb movements during different kind of locomotion (swimming, walking, hindlimb swimming but forelimb walking) was performed. After deafferentation an increase of the locomotor rhythm frequency and a decrease of the movement amplitude of hindlimb joints were common features for all kinds of the locomotion. This indicates that the above parameters of locomotor movements were formed by afferent influences. A decrease of the movement amplitude and of the EMG activity which were evoked after deafferentation were minimal for swimming and maximal for walking. The role of afferent influences in formation of different locomotion patterns is discussed.     

One day of motor training with amphetamine impairs motor recovery following spinal cord injury

It has previously been reported that a single dose of amphetamine paired with training on a beam walking task can enhance locomotor recovery following brain injury (Feeney et al., 1982). Here, we investigated whether this same drug/training regimen could enhance functional recovery following either thoracic (T9) or cervical (C5) spinal cord injury. Different groups of female Sprague-Dawley rats were trained on a beam walking task, and in a straight alley for assessment of hindlimb locomotor recovery using the BBB locomotor scale. For rats that received C5 hemisections, forelimb grip strength was assessed using a grip strength meter. Three separate experiments assessed the consequences of training rats on the beam walking task 24 h following a thoracic lateral hemisection with administration of either amphetamine or saline. Beginning 1 h following drug administration, rats either received additional testing/retraining on the beam hourly for 6 h, or they were returned to their home cages without further testing/retraining. Rats with thoracic spinal cord injuries that received amphetamine in conjunction with testing/retraining on the beam at 1 day post injury (DPI) exhibited significantly impaired recovery on the beam walking task and BBB. Rats with cervical spinal cord injuries that received training with amphetamine also exhibited significant impairments in beam walking and locomotion, as well as impairments in gripping and reaching abilities. Even when administered at 14 DPI, the drug/training regimen significantly impaired reaching ability in cervical spinal cord injured rats. Impairments were not seen in rats that received amphetamine without training. Histological analyses revealed that rats that received training with amphetamine had significantly larger lesions than saline controls. These data indicate that an amphetamine/training regimen that improves recovery after cortical injury has the opposite effect of impairing recovery following spinal cord injury because early training with amphetamine increases lesion severity.     

Blockade of group II, but not group I, mGluRs in the rat nucleus accumbens inhibits the expression of conditioned hyperactivity in an amphetamine-associated environment

Environmental stimuli associated with amphetamine (AMPH) can elicit conditioned locomotion in rats, and the nucleus accumbens (NAcc) is known to be important in this process. This study examined the contribution of metabotropic glutamate receptors (mGluRs) in the NAcc to the expression of conditioned locomotion in an AMPH-associated environment. Rats in different groups were administered injections in five 3-day blocks: Paired, AMPH (1.0mg/kg, IP) in locomotor activity boxes on day 1 and saline in their home cages on day 2; Unpaired, saline in the activity boxes on day 1 and AMPH in their home cages on day 2; or Control, saline in both environments. No injections were administered on day 3 of each block. One week after the last conditioning block, all rats were tested for their conditioned locomotor response in the activity boxes for 1h following an IP saline injection. In Paired rats, this injection was preceded by a bilateral microinjection into the NAcc of saline, the group I mGluR antagonist, AIDA (0.5, 5.0 nmol/side), or the group II mGluR antagonist, EGLU (0.5, 5.0 nmol/side). Unpaired and Control rats received NAcc saline. As expected, Paired rats showed both increased locomotor activity and rearing compared to rats in either the Unpaired or Control groups. However, the expression of this conditioned hyper-locomotion was dose-dependently inhibited by NAcc EGLU, but not by AIDA. These results suggest that activation of group II, but not of group I, mGluRs in the NAcc contributes to the expression of conditioned locomotion in an environment associated with amphetamine.     

Effect of vigabatrin (gamma-vinyl GABA) on amino acid levels in CSF of epileptic patients.

Vigabatrin (gamma-vinyl GABA) is a new anticonvulsive drug that irreversibly inhibits the activity of GABA transaminase. The effect of vigabatrin on neurotransmission-related amino acids in CSF of 28 epileptic patients was studied and the relationship between the amino acid pattern and clinical response during 7 months of administration of vigabatrin. Of this study population, 46% had more than 50% decrease in seizure frequency (responders). In 54% the seizures decreased less than 50% (nonresponders). In the whole study group, the levels of total GABA during vigabatrin treatment were 283%, free GABA 197%, homocarnosine 310% and glycine 128% that of the levels at baseline in the same patients. Glutamate, glutamine, aspartate, asparagine, and taurine concentrations did not change. The amino acid pattern in CSF during administration of vigabatrin did not differ significantly in responders and nonresponders. The study suggests that both GABAergic and glycinergic neurotransmission are affected by vigabatrin. The changes in CSF levels of neurotransmitter amino acids are, however, not necessarily related to the clinical response.