- Email: [email protected]
P.1.b.009 Effects of Chlorpromazine on GIRK channel expressed transiently in HEK cells
P.l.b Basic and clinical neuroscience - Neuroanatomy and neurophysiology catalytic activity of hepatic hCESl in individuals spanning the lifecycle from neonates though the elderly revealed significant differences. Subject samples representing ages 13 days, 1 month, 3-8 months, 1-4 years, 6-9 years, 12-18 years, and 75-85 years was 9.9%, 12.5%, 66.6±7.8%, 70.4±20.0%, 123.2±84.3%, 1l1.0±50.0%, and 1l0.9±41.2, respectively, when compared to the pooled sample values. The relative activity of hCES2 was estimated to be 66.5%, 27.1%, 68.3±22.6%, 84.1±39.6%, 91.1±29.7%, 102.3±4.9%, and 94.6±36.2% in the liver s9 samples of the subjects with the ages of 13 days, 1 month, 3-8 months, 1-4 years, 6-9 years, 12-18 years, and 75-85 years, respectively. Additionally, the expression and activity of mCES 1 and mCES2 were not significantly altered after the animals were treated with human growth hormone, indicating growth hormone may not be associated with the low level of CES expression during early developmental stages. In conclusion, we demonstrated that expression and activity of the major hydrolytic enzymes hCES 1 and hCES2 in the human liver were significantly lower in the subjects during their early developmental period relative to adults. Pediatric patients may not metabolize hCES 1 and hCES2 substrate drugs as efficiently as adults. Thus, appropriate dose adjustments could be necessary for the children during the treatment of medications metabolized by hCESl and/or hCES2.
Ip.1.b.ooal
Hypothalamic-pituitary-thyroid (HPT) axis and personality traits in attempted suicide
J. Jokinen 1 ., C. Sinai 1, P. Nordstrom1 . 1Karolinska Institute, Department of Clinical Neuroscience, Stockholm, Sweden Background: Studies relating thyroid hormones to personality traits are few and mainly focused on forensic psychiatric populations. In delinquent male participants, the association between thyroid hormones and psychopathy- and aggression-related personality traits has been found (Stalenheim 2004). Plasma T3 levels have recently been reported to show a negative correlation with the Beck Suicide Intent Scale and the Montgomery Asberg Depression Rating Scale in male suicide attempters (Jokinen et aI., 2008). The suicidal temperament hypothesis suggests that certain personality traits may render an individual vulnerable to the risk of suicide. Features of suicidal temperament include such personality traits as anger and aggression, anxiety proneness, impulsivity and low socialization as well as being socially introverted, depressed and psychasthenic. The aim of the study was to investigate personality traits, using the Karolinska Scales of Personality (KSP) in relation to hormones in the HPT axis in 100 euthyreoid suicide attempters. Patients having their clinical follow-up after attempted suicide at the Suicide Prevention Clinic of the Karolinska University Hospital were invited to participate in the study of biological and psychological risk factors for suicidal behavior. Patients were recruited during 2001-2005. Method: Standard multiple regression analyses were conducted with TSH, T3, T4 and T31T4 ratio respectively, as the dependent variable and KSP factors (Anxiety Proneness, Aggressiveness, and Impulsivity) and subscales (Detachment, Social Desirability, and Socialization) as independent variables. The results were controlled for use of antidepressant medication and of alcohol consumption. Results:For males, the R for regression of the T3/T4 ratio (n=28) was significantly different from zero F(7,15)=5.95,
S245
p < 0.002, with R2 at 0.74. The adjusted R2 value of 0.61 indicates that 61% of the variability in the T3/T4 ratio was predicted by the model. Two regression coefficients were statistically significant predictors of the T3/T4 ratio in the regression model; Aggressiveness, p = 0.003, and Detachment, p = 0.004. The size and direction of the relationships suggest that a low T3/T4 ratio was associated with high scores on the trait Aggressiveness and low scores on Detachment. The aggressiveness score was the most important predictor as indicated by the high ~ value. There was a gender difference in thyroid hormones and personality traits. In the female group the regression model of the T3/T4 ratio did not reach, but approached, statistical significance and a low T3/T4 ratio was associated with low Anxiety Proneness and high Social Desirability. Conclusions: Suicide attempters exhibit greater lifetime aggression and our finding is discussed in relation to earlier studies of male forensic psychiatric populations. HPT axis may be related via personality trait Aggressiveness to suicidal behaviour in men.
References [I] Stalenheim, E. G., 2004. Long-term validity of biological markers of psychopathy and criminal recidivism: follow-up 6-8 years after forensic psychiatric investigation. Psychiatry Res. 121,281-91. [2] Jokinen, 1., Samuelsson, M., Nordstrom, A. L., Nordstrom, P., 2008. HPT axis, CSF monoamine metabolites, suicide intent and depression severity in male suicide attempters. J Affect Disord. 111, 119-24.
1P.1.b.0091 Effects of Chlorpromazine on
GIRK channel expressed transiently in HEK cells
E. Kim 1 ., K. Kim 1, S. Hyun1 . 1KoreaInstituteojToxicology, Pharmacology, Taejon, South-Knrea G-protein-gated, inward rectifying K+ (GIRK) channels are complexes consisting ofGIRK subunits. Four GIRK subunits (GIRK1GIRK4) have been identified and can form homotetrameric and heterotetrameric channels. GIRKlIGIRK4 channels are found in the heart and mediate the heart rate decrease caused by parasympathetic discharge, whereas channels formed by various combinations of GIRK1, GIRK2 and GIRK3 mediate inhibition in the nervous system. Most of all, GIRKlIGIRK2 channels is found throughout the CNS, in which they contribute to the postsynaptic inhibition triggered by many neurotransmitters and plays a central role in thermal nociception. Chlorpromazine is one of phenothiazine drugs. Adverse effects of Central nervous system (CNS) from phenothiazine drugs are common. However, the effects of many of the chlorpromazine on GIRK channel expressed in mammalian cell lines remain unknown. In the present study, we examined the effect of chlorpromazine on GIRK channel (especially GIRKlIGIRK2) currents using the whole- cell voltage clamp technique. Transiently transfected Human embryonic kidney (HEK) cells expressing GIRK (GIRKlIGIRK2) channel were used for the investigation. KCNJ3 cDNA and KCNJ6 cDNA in pCMV6-XL4 expression vector (purchased from Origene INC, USA) were cotransfected with the surface marker protein, green fluorescence protein (GFP) to allow assessment of the transfection efficiency and identification. The plasmid was sequenced and subsequently introduced into cells using lipofectAmin2000 (Gibco BRL, USA) as a transfection reagent. Ionic currents were recorded in whole-cell configuration using an EPC8 amplifier (HEKA INC, Germany). After the data were digitized and analyzed using an EPC8 AD converter (HEKA INC, Germany) at a sampling rate of 5 kHz, they were low-pass filtered at 1 kHz. GIRK channel
P.l.b Basic and clinical neuroscience - Neuroanatomy and neurophysiology
S246
current was induced by single 1000-ms voltage pulse to -150 mV from the holding potential of -80 mV once every 10 s. The composition of extracellular solution was (in mM): NaCl, 143; KCl, 5.4; CaC12, 1.8; MgCI2, 0.5; HEPES, 5; NaH2P04, 0.33; glucose, 10 (adjusted to pH 7.4 with NaOH). The internal solution (pipette) for measurement of GIRK channel currents contained (in mM): K-ASp, 130; KCl, 15; EGTA, 5; HEPES, 10; MgCI2, 1; Na2-ATp, 5 (adjusted to pH 7.25 with KOH). All chemicals were obtained from Sigma-Aldrich Co. (MO, USA). First of all, we confirmed GIRK channel currents expressed in HEK cells by using positive control, clozapine. Clozapine at concentration of 30 !.t. blocked GIRK channel currents by about 87.5%. When we examined the effect of chlorpromazine on GIRK channel currents, we observed that chlorpromazine blocked GIRK channel currents stably expressed in HEK cells. Concentration-response relationships for chlorpromazine on GIRK channel blockade were obtained for various concentrations (1, 10 and 30 !.t.). Chlorpromazine at respective concentration inhibited GIRK channelby 40.2, 68.5 and 89.2%. Application of the Hill equation revealed an IC50 of 2.04±0.71 !.t. and a Hill coefficient of 0.63±0.I5.
1P.1.b.0101 The P3a component of the event-related potential from passive visual task in patients with schizophrenia Jeon1 "
Yi2 ,
In active paradigm, the P3a and P3b were successfully acquired in all 35 control subjects (100%), but in only 35 patients (75%). In passive paradigm, the P3a was elicited for 45 patients (90%) as well as for 35 control subjects (100%). Passive P3a (F=3.7, p = 0.08 in amplitude, F = 32, P < 0.0001 in latency), active P3a (F = 12.6, P = 0.001 in amplitude, F = 25, P < 0.0001 in latency), and active P3b (F=2.6, p=0.09 in amplitude, F = 14.3, P < 0.001)) were smaller and delayed in patients with schizophrenia. With using mixed between (groups) and within (anterior-posterior and laterality) repeated measurement ANOVA, the P300 components showed topographic differences between two groups (F = 4.4, p=0.03 in passive P3a, F=5.7, p=O.OOI in active P3a, and F=5.4, p=O.OI in active P3b). The passive 3 stimulus visual P300 paradigm could be used for further exploring the patients with schizophrenia without or minimizing losing the information from some patients who are uncooperative with using only the conventional active P300 paradigms. References
[1] Jeon YW, Polich J 2001. P3a from a passive visual stimulus task. C1in Neurophysiol. 112(12):2202-8 [2] Polich J, McIsaac HK. 1994. Comparison of auditory P300 habituation from active and passive conditions. Int J Psychophysio1 17:25-34.
1P.1.b.0111 Histamine H3 receptor activation decreases gamma oscillation power and causes desynchronization of action potentials
1Incheon St. Mary's E. Park1, J. S. Kim3 . Hospital, Dept ofpsychiatry, Inchon, South-IWrea; 2Kangnam Sacred Heart Hospital, Dept ofpsychiatry, Seoul, South-IWrea; 3Guro Hospital, Dept ofpsychiatry, Seoul, South-Korea
R. Andersson1 " A. Fisahn1 , M. Lindskog1 . 1Karolinska Institute, Department of Neuroscience, Stockholm, Sweden
The paradigm effects were not enough to be elucidated, even though it is well known that the event-related potential P300 was useful for exploring schizophrenia. Most P300 studies require the subject to actively respond to the target stimulus, but P300-like waveforms also can be elicited with 'passive' auditory paradigms in which an intentional discrimination between the two tones is not required. These methods are of clinical interest, since they can be used with non-compliant subjects such as young children, individuals with demented illness, and difficult psychiatric patients. However, most passive auditory tasks elicit altered P300 components compared to those elicited by active processing. Indeed, conventional visual stimuli presented under passive viewing conditions can not elicit reliable P300 components because the attentional demands of a visual target in an oddball sequence are not compelling relative to the alerting qualities of an infrequent auditory target stimulus. Thus, passive and active paradigms can produce P300 waveforms because component outcomes are determined by the eliciting stimuli if only when their physical qualities coerce attentional engagement. This study was designed to examine that visual passive paradigm is appropriate for relatively uncooperative and admitted patients with schizophrenia. Visual 3 stimulus oddball paradigm was employed for admitted patients with schizophrenia (N = 50) and controls (N = 35). For the patients, the symptoms severity was assessed by Positive and negative syndrome scale (PANSS). The paradigm was composed of standard (small circle, 80%), distractors (large rectangle, 10%), and targets (large circle, 10%) in a random manner once every 2 s. The passive task was presented first, and the subjects were instructed to look at the monitor in relaxed manner. The active task was presented in second session, and subjects were asked to press a mouse button to the targets. P3a to the distractors is elicited in passive and active tasks. P3b to the targets is elicited in active task.
The histamine system of the central nervous system is heavily involved in arousal and wakefulness, thus affecting cognitive functions. Histaminergic neurons project to all areas of the brain, and dense innervation is found in the neocortex and the hippocampus [1]. So far 4 histamine receptors have been identified and recently the histamine H3 receptor in particular has received considerable interest as a potential target for procognitive drugs. Rhythmical activity in neocortex and the hippocampus are correlated with cognitive activity such as memory formation, recall and direction of attention. Of particular interest are field potential oscillations in the gamma frequency band (20-80 Hz) since oscillation at this frequency is disrupted in disorders such as schizophrenia [2]. In the present work we study the direct effect of histamine H3 receptor activation on kainate induced gamma oscillations in the rat hippocampal slice in the pyramidal cell layer in the CA3 area. Experiments were carried out in horizontal hippocampal slices from Sprague-Dawley rats (pI5-P22). Gamma oscillations were induced by perfusion of 100 nM kainate and electrophysiolgical field and patch recordings were made in Stratum pyramidale of the CA3 field of hippocampus [3]. Fast Fourier Transformations for power spectra were computed and power was calculated as the integrated power spectrum between 20-80 Hz. Stimulating the H3 receptor with the agonist R-a-Methylhistamine (RAMH) at 100 nM decreases kainate induced gamma oscillation power (60.5± 14.0 % of initial kainate oscillation) but did not change the peak frequency (kainate: 29.8±0.64 Hz; RAMH 30.3±1.35 Hz). The specificity of this effect was confirmed by a H3 receptor antagonist, which completely blocked the inhibition caused by RAMH. This decrease in power of gamma oscillations is not caused by a decrease in excitatory or inhibitory post-synaptic currents, as we do not detect any difference in either amplitude or
y.
Ip.1.b.ooal
Hypothalamic-pituitary-thyroid (HPT) axis and personality traits in attempted suicide
J. Jokinen 1 ., C. Sinai 1, P. Nordstrom1 . 1Karolinska Institute, Department of Clinical Neuroscience, Stockholm, Sweden Background: Studies relating thyroid hormones to personality traits are few and mainly focused on forensic psychiatric populations. In delinquent male participants, the association between thyroid hormones and psychopathy- and aggression-related personality traits has been found (Stalenheim 2004). Plasma T3 levels have recently been reported to show a negative correlation with the Beck Suicide Intent Scale and the Montgomery Asberg Depression Rating Scale in male suicide attempters (Jokinen et aI., 2008). The suicidal temperament hypothesis suggests that certain personality traits may render an individual vulnerable to the risk of suicide. Features of suicidal temperament include such personality traits as anger and aggression, anxiety proneness, impulsivity and low socialization as well as being socially introverted, depressed and psychasthenic. The aim of the study was to investigate personality traits, using the Karolinska Scales of Personality (KSP) in relation to hormones in the HPT axis in 100 euthyreoid suicide attempters. Patients having their clinical follow-up after attempted suicide at the Suicide Prevention Clinic of the Karolinska University Hospital were invited to participate in the study of biological and psychological risk factors for suicidal behavior. Patients were recruited during 2001-2005. Method: Standard multiple regression analyses were conducted with TSH, T3, T4 and T31T4 ratio respectively, as the dependent variable and KSP factors (Anxiety Proneness, Aggressiveness, and Impulsivity) and subscales (Detachment, Social Desirability, and Socialization) as independent variables. The results were controlled for use of antidepressant medication and of alcohol consumption. Results:For males, the R for regression of the T3/T4 ratio (n=28) was significantly different from zero F(7,15)=5.95,
S245
p < 0.002, with R2 at 0.74. The adjusted R2 value of 0.61 indicates that 61% of the variability in the T3/T4 ratio was predicted by the model. Two regression coefficients were statistically significant predictors of the T3/T4 ratio in the regression model; Aggressiveness, p = 0.003, and Detachment, p = 0.004. The size and direction of the relationships suggest that a low T3/T4 ratio was associated with high scores on the trait Aggressiveness and low scores on Detachment. The aggressiveness score was the most important predictor as indicated by the high ~ value. There was a gender difference in thyroid hormones and personality traits. In the female group the regression model of the T3/T4 ratio did not reach, but approached, statistical significance and a low T3/T4 ratio was associated with low Anxiety Proneness and high Social Desirability. Conclusions: Suicide attempters exhibit greater lifetime aggression and our finding is discussed in relation to earlier studies of male forensic psychiatric populations. HPT axis may be related via personality trait Aggressiveness to suicidal behaviour in men.
References [I] Stalenheim, E. G., 2004. Long-term validity of biological markers of psychopathy and criminal recidivism: follow-up 6-8 years after forensic psychiatric investigation. Psychiatry Res. 121,281-91. [2] Jokinen, 1., Samuelsson, M., Nordstrom, A. L., Nordstrom, P., 2008. HPT axis, CSF monoamine metabolites, suicide intent and depression severity in male suicide attempters. J Affect Disord. 111, 119-24.
1P.1.b.0091 Effects of Chlorpromazine on
GIRK channel expressed transiently in HEK cells
E. Kim 1 ., K. Kim 1, S. Hyun1 . 1KoreaInstituteojToxicology, Pharmacology, Taejon, South-Knrea G-protein-gated, inward rectifying K+ (GIRK) channels are complexes consisting ofGIRK subunits. Four GIRK subunits (GIRK1GIRK4) have been identified and can form homotetrameric and heterotetrameric channels. GIRKlIGIRK4 channels are found in the heart and mediate the heart rate decrease caused by parasympathetic discharge, whereas channels formed by various combinations of GIRK1, GIRK2 and GIRK3 mediate inhibition in the nervous system. Most of all, GIRKlIGIRK2 channels is found throughout the CNS, in which they contribute to the postsynaptic inhibition triggered by many neurotransmitters and plays a central role in thermal nociception. Chlorpromazine is one of phenothiazine drugs. Adverse effects of Central nervous system (CNS) from phenothiazine drugs are common. However, the effects of many of the chlorpromazine on GIRK channel expressed in mammalian cell lines remain unknown. In the present study, we examined the effect of chlorpromazine on GIRK channel (especially GIRKlIGIRK2) currents using the whole- cell voltage clamp technique. Transiently transfected Human embryonic kidney (HEK) cells expressing GIRK (GIRKlIGIRK2) channel were used for the investigation. KCNJ3 cDNA and KCNJ6 cDNA in pCMV6-XL4 expression vector (purchased from Origene INC, USA) were cotransfected with the surface marker protein, green fluorescence protein (GFP) to allow assessment of the transfection efficiency and identification. The plasmid was sequenced and subsequently introduced into cells using lipofectAmin2000 (Gibco BRL, USA) as a transfection reagent. Ionic currents were recorded in whole-cell configuration using an EPC8 amplifier (HEKA INC, Germany). After the data were digitized and analyzed using an EPC8 AD converter (HEKA INC, Germany) at a sampling rate of 5 kHz, they were low-pass filtered at 1 kHz. GIRK channel
P.l.b Basic and clinical neuroscience - Neuroanatomy and neurophysiology
S246
current was induced by single 1000-ms voltage pulse to -150 mV from the holding potential of -80 mV once every 10 s. The composition of extracellular solution was (in mM): NaCl, 143; KCl, 5.4; CaC12, 1.8; MgCI2, 0.5; HEPES, 5; NaH2P04, 0.33; glucose, 10 (adjusted to pH 7.4 with NaOH). The internal solution (pipette) for measurement of GIRK channel currents contained (in mM): K-ASp, 130; KCl, 15; EGTA, 5; HEPES, 10; MgCI2, 1; Na2-ATp, 5 (adjusted to pH 7.25 with KOH). All chemicals were obtained from Sigma-Aldrich Co. (MO, USA). First of all, we confirmed GIRK channel currents expressed in HEK cells by using positive control, clozapine. Clozapine at concentration of 30 !.t. blocked GIRK channel currents by about 87.5%. When we examined the effect of chlorpromazine on GIRK channel currents, we observed that chlorpromazine blocked GIRK channel currents stably expressed in HEK cells. Concentration-response relationships for chlorpromazine on GIRK channel blockade were obtained for various concentrations (1, 10 and 30 !.t.). Chlorpromazine at respective concentration inhibited GIRK channelby 40.2, 68.5 and 89.2%. Application of the Hill equation revealed an IC50 of 2.04±0.71 !.t. and a Hill coefficient of 0.63±0.I5.
1P.1.b.0101 The P3a component of the event-related potential from passive visual task in patients with schizophrenia Jeon1 "
Yi2 ,
In active paradigm, the P3a and P3b were successfully acquired in all 35 control subjects (100%), but in only 35 patients (75%). In passive paradigm, the P3a was elicited for 45 patients (90%) as well as for 35 control subjects (100%). Passive P3a (F=3.7, p = 0.08 in amplitude, F = 32, P < 0.0001 in latency), active P3a (F = 12.6, P = 0.001 in amplitude, F = 25, P < 0.0001 in latency), and active P3b (F=2.6, p=0.09 in amplitude, F = 14.3, P < 0.001)) were smaller and delayed in patients with schizophrenia. With using mixed between (groups) and within (anterior-posterior and laterality) repeated measurement ANOVA, the P300 components showed topographic differences between two groups (F = 4.4, p=0.03 in passive P3a, F=5.7, p=O.OOI in active P3a, and F=5.4, p=O.OI in active P3b). The passive 3 stimulus visual P300 paradigm could be used for further exploring the patients with schizophrenia without or minimizing losing the information from some patients who are uncooperative with using only the conventional active P300 paradigms. References
[1] Jeon YW, Polich J 2001. P3a from a passive visual stimulus task. C1in Neurophysiol. 112(12):2202-8 [2] Polich J, McIsaac HK. 1994. Comparison of auditory P300 habituation from active and passive conditions. Int J Psychophysio1 17:25-34.
1P.1.b.0111 Histamine H3 receptor activation decreases gamma oscillation power and causes desynchronization of action potentials
1Incheon St. Mary's E. Park1, J. S. Kim3 . Hospital, Dept ofpsychiatry, Inchon, South-IWrea; 2Kangnam Sacred Heart Hospital, Dept ofpsychiatry, Seoul, South-IWrea; 3Guro Hospital, Dept ofpsychiatry, Seoul, South-Korea
R. Andersson1 " A. Fisahn1 , M. Lindskog1 . 1Karolinska Institute, Department of Neuroscience, Stockholm, Sweden
The paradigm effects were not enough to be elucidated, even though it is well known that the event-related potential P300 was useful for exploring schizophrenia. Most P300 studies require the subject to actively respond to the target stimulus, but P300-like waveforms also can be elicited with 'passive' auditory paradigms in which an intentional discrimination between the two tones is not required. These methods are of clinical interest, since they can be used with non-compliant subjects such as young children, individuals with demented illness, and difficult psychiatric patients. However, most passive auditory tasks elicit altered P300 components compared to those elicited by active processing. Indeed, conventional visual stimuli presented under passive viewing conditions can not elicit reliable P300 components because the attentional demands of a visual target in an oddball sequence are not compelling relative to the alerting qualities of an infrequent auditory target stimulus. Thus, passive and active paradigms can produce P300 waveforms because component outcomes are determined by the eliciting stimuli if only when their physical qualities coerce attentional engagement. This study was designed to examine that visual passive paradigm is appropriate for relatively uncooperative and admitted patients with schizophrenia. Visual 3 stimulus oddball paradigm was employed for admitted patients with schizophrenia (N = 50) and controls (N = 35). For the patients, the symptoms severity was assessed by Positive and negative syndrome scale (PANSS). The paradigm was composed of standard (small circle, 80%), distractors (large rectangle, 10%), and targets (large circle, 10%) in a random manner once every 2 s. The passive task was presented first, and the subjects were instructed to look at the monitor in relaxed manner. The active task was presented in second session, and subjects were asked to press a mouse button to the targets. P3a to the distractors is elicited in passive and active tasks. P3b to the targets is elicited in active task.
The histamine system of the central nervous system is heavily involved in arousal and wakefulness, thus affecting cognitive functions. Histaminergic neurons project to all areas of the brain, and dense innervation is found in the neocortex and the hippocampus [1]. So far 4 histamine receptors have been identified and recently the histamine H3 receptor in particular has received considerable interest as a potential target for procognitive drugs. Rhythmical activity in neocortex and the hippocampus are correlated with cognitive activity such as memory formation, recall and direction of attention. Of particular interest are field potential oscillations in the gamma frequency band (20-80 Hz) since oscillation at this frequency is disrupted in disorders such as schizophrenia [2]. In the present work we study the direct effect of histamine H3 receptor activation on kainate induced gamma oscillations in the rat hippocampal slice in the pyramidal cell layer in the CA3 area. Experiments were carried out in horizontal hippocampal slices from Sprague-Dawley rats (pI5-P22). Gamma oscillations were induced by perfusion of 100 nM kainate and electrophysiolgical field and patch recordings were made in Stratum pyramidale of the CA3 field of hippocampus [3]. Fast Fourier Transformations for power spectra were computed and power was calculated as the integrated power spectrum between 20-80 Hz. Stimulating the H3 receptor with the agonist R-a-Methylhistamine (RAMH) at 100 nM decreases kainate induced gamma oscillation power (60.5± 14.0 % of initial kainate oscillation) but did not change the peak frequency (kainate: 29.8±0.64 Hz; RAMH 30.3±1.35 Hz). The specificity of this effect was confirmed by a H3 receptor antagonist, which completely blocked the inhibition caused by RAMH. This decrease in power of gamma oscillations is not caused by a decrease in excitatory or inhibitory post-synaptic currents, as we do not detect any difference in either amplitude or
y.