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Objective: It is clinically known that compared to typical antipsychotics, the atypical antipsychotics are likely more efficient in the treatment of psychosis with negative symptoms and cause fewer extrapyramidal side effects. In the differentiation of receptors and extrapyramidal system (EPS) side effects, there are some medications which cannot be classified as typical or atypical antipsychotics according to their activity at D2 receptors. There is not a clear method to classify antipsychotics.
Materials & Methods: The experiments performed in this study were carried out according to the rules in the Guide for the Care and Use of Laboratory Animals adopted by the National Institutes of Health (U.S.A) and received Ege University Animal Ethics Committee's consent. (Approval number: 2010-081) In this study, 9 Sprague-Dawley (450-500 g) adult male rats (16-20 weeks old) were used. The rats were maintained under controlled environmental conditions throughout the study: 21-25 °C ambient temperature, 12:12 light-dark cycle (light from 7:00-19:00h), and Standard laboratory food and tap water available ad libitum. Under anesthesia, a small hole was drilled. Then by using the bregma as a reference for the stereotaxic method (coordinates Anteroposterior: - 2.8 mm, Lateral: + 4.8 mm, Ventral: - 8.5 mm) (Paxinos Rat Brain), an exterior insulated bipolar EEG electrode was placed in the basolateral amygdala. The electrodes were fixed by using a dental acrylic (numerous alloys are used in the making of dental restorations). Rats were anesthetized by using ketamine (40 mg/kg) and xylazine (4 mg/kg) intraperitoneally (IP). Three days after the electrode was fixed, spontaneous amygdala EEG records were taken from the rats by injecting saline, when they were awake and in their own box. Subsequently at 7 days intervals (5 times more than the half life of the drugs), olanzapine 1 mg/kg, haloperidol 1 mg/kg, chlorpromazine 5 mg/kg or ziprasidone 1 mg/kg doses were IP administered. Before each drug injection amygdalar EEG records were taken to observe the baseline rhythm of the amygdala. These drug doses were chosen after consideration of the hypermetobolism of rats. EEG recording was started 30 minutes after drug injection and each rat was recorded for 20 minutes. Signals were amplified by 10,000 times and filtered within a range of 1-60 Hz. System records were taken by a Biopac MP30 amplifier system and evaluated with FFT (Fast Fourier Transform) and PSA (Power Spectral Analyses) methods. During this process Delta 1-4 Hz, Theta 4-8 Hz, alpha 8-12 Hz and beta 12-20 Hz waves in the EEG are accepted as the ratio of percentage in PSA (Power Spectral Analyses) methods. We confirmed electrode locations histologically following euthanisation.
Results: According to the data obtained, the perceptibly dominant frequency in amygdala spontaneous activity was founded to be 1-4 Hz (Delta). When we compared the EEG records in the 1-4 Hz (Delta) band of the groups which were given typical and atypical antipsychotic drugs to the control group given isotonic saline, there was significant (p < 0.005) inhibition. On the other hand in the 4-8 Hz (Theta) and the 8-12 Hz (Alpha) (Figure 4) bands, a significant (p < 0.005) increase was observed. When the EEG records of the group which was given atypical antipsychotics were compared to the typical antipsychotic administered groups, in the 1-4 Hz band a significant increase (p< 0.05) and in the 4-8 Hz and 8-12 Hz bands significant inhibition (p<0.05) was observed. In addition, the EEG records of the atypical antipsychotic groups were nearer to those of the saline administered group.
Conclusions: The results showed that there was less change in spontaneous electrical activity of the basolateral amygdala in the atypical antipsychotic groups than in the typical antipsychotic ones. The EEG of deep brain recording may be used as a new method for classifying antipsychotics into different groups. Improvements in cognitive function in schizophrenia with atypical antipsychotics are known. This effect may be due to the impact of atypical antipsychotics on the amygdala. This effect is probably related to the fast-off theory, meaning that the drug binds and leaves the receptor quickly. Although mesolimbic dopaminergic hyperactivation is inhibited with antipsychotics, the correction of mesocortical dopaminergic hypoactivation and the recovery of cognitive capacity and normal affect are not completely clarified. There are extensive connections between the prefrontal cortex and the amygdala. Typical antipsychotics in this study increased the frequency of firing in the amygdala. This effect may be interpreted as being similar to the effects of Parkinsonism caused by the blockade of striatal D2 receptors. In this study typical antipsychotics increased the amygdalar frequency of the EEG. The breakdown of frequency of the amygdala was more pronounced in chlorpromazine administration. This effect of chlorpromazine may be associated with non-selective blockade of the histaminergic, adrenergic, serotonergic, and dopaminergic systems. Atypical antipsychotics caused a very small change in the basal rhythm of the amygdala (Delta Frequency). This effect is thought to be related to the recovery of normal cognitive function during use of the atypical antipsychotic drugs. In future studies, the effects of antipsychotics in different brain regions may lead to a better differentiation of the typical and atypical antipsychotics.