[Singing Voice Handicap Index-12 : Development and validation of a German version]. / Der Singing Voice Handicap Index-12 : Entwicklung und Validierung einer deutschen Fassung.

BACKGROUND: The aim of this study was to develop a shortened German version of the Singing Voice Handicap Index (SVHI). The SVHI is a one-dimensional instrument for self-assessment of a voice disorder in singers. The questionnaire developed in the USA comprises 36 items and has been available in a validated German version since 2013. METHODS: Bicentric data from a total of 200 patients formed the basis for item analysis and selection. Using corrected item-total correlations, 12 items were selected for the abridged version. The internal consistency was calculated. The SVHI-12 was subsequently validated in 97 vocal patients and 105 vocally healthy singers (control group) using the test-retest procedure. RESULTS: The SVHI-12 achieved a good internal consistency (Cronbach's alpha = 0.93) and a good test-retest reliability (intra-class correlation r = 0.88 ; p < 0.001). The patients had significantly higher overall scores (18 ± 13 vs. 7 ± 6) compared to the healthy control group. The SVHI-12 overall score correlated significantly positively with the severity of the voice disorder as reported by the patient (r = 0.68; p < 0.001). As a threshold value above which a voice can be described as disturbed, a total score > 7 points was calculated using receiver operating curve analysis. As an indication of a voice disorder, a sensitivity of 81% and a specificity of 71% is thus achieved (Youden index 0.523, area under the curve 0.827, 95% confidence interval 0.769-0.885). CONCLUSION: The shortened SVHI has similarly good psychometric characteristics to the original SVHI. With the SVHI-12, a valid and effective instrument for the detection of singing voice disorders is available for German-speaking countries.

Effects of dark chocolate consumption on the prothrombotic response to acute psychosocial stress in healthy men.

Flavanoid-rich dark chocolate consumption benefits cardiovascular health, but underlying mechanisms are elusive. We investigated the acute effect of dark chocolate on the reactivity of prothrombotic measures to psychosocial stress. Healthy men aged 20-50 years (mean ± SD: 35.7 ± 8.8) were assigned to a single serving of either 50 g of flavonoid-rich dark chocolate (n=31) or 50 g of optically identical flavonoid-free placebo chocolate (n=34). Two hours after chocolate consumption, both groups underwent an acute standardised psychosocial stress task combining public speaking and mental arithmetic. We determined plasma levels of four stress-responsive prothrombotic measures (i. e., fibrinogen, clotting factor VIII activity, von Willebrand Factor antigen, fibrin D-dimer) prior to chocolate consumption, immediately before and after stress, and at 10 minutes and 20 minutes after stress cessation. We also measured the flavonoid epicatechin, and the catecholamines epinephrine and norepinephrine in plasma. The dark chocolate group showed a significantly attenuated stress reactivity of the hypercoagulability marker D-dimer (F=3.87, p=0.017) relative to the placebo chocolate group. Moreover, the blunted D-dimer stress reactivity related to higher plasma levels of the flavonoid epicatechin assessed before stress (F=3.32, p = 0.031) but not to stress-induced changes in catecholamines (p's=0.35). There were no significant group differences in the other coagulation measures (p's≥0.87). Adjustments for covariates did not alter these findings. In conclusion, our findings indicate that a single consumption of flavonoid-rich dark chocolate blunted the acute prothrombotic response to psychosocial stress, thereby perhaps mitigating the risk of acute coronary syndromes triggered by emotional stress.

[Universal newborn hearing screening (UNHS): is it possible to successfully implement it nationwide?]. / Universelles Neugeborenen-Hörscreening (UNHS) - Ist eine erfolgreiche Umsetzung flächendeckend möglich?

BACKGROUND: Since 01.01.2009 in Germany a newborn hearing screening (UNHS) is obligatory for every child. The UNHS is part of the guidelines for the prevention of diseases for children up to 6 years of age (Kinder-Richtlinien). 2 years after its introduction in Bavaria, we now evaluate whether the UNHS has been implemented successfully,and if the quality criteria of the guidelines have been met. METHODS: In the guidelines details for the procedure and screening quality are given. The UNHS data from the screening facilities in Bavaria were evaluated for process quality criteria like screening coverage, screening method, REFER rate (rate of failed tests) and child age at diagnosis. RESULTS: More than 96 % of all newborns were screened. The REFER rate for 2010 was 4.5 %. Only 18 % of the controls were done by a paediatric audiologist.In 38.5 % of the newborns an intervention of the screening centre was necessary to assure controlling of a failed screening test. In 2009 the median age at diagnosis for a bilateral hearing loss was 5.5 months, and the start of therapy was 6.2 months. CONCLUSION: In Bavaria the UNHS was implemented successfully. A tracking system for all children who failed the hearing screening test is pivotal for the early diagnosis of children with bilateral hearing deficiency.

[Questionnaire on auditory perception disorders: psychometric correlates in preschool children]. / Anamnesebogen für auditive Verarbeitungs- und Wahrnehmungsstörungen : Psychometrische Korrelate im Vorschulalter.

BACKGROUND: A standardized questionnaire on central auditory processing disorders ["Anamnesebogen zur Erfassung auditiver Verarbeitungs- und Wahrnehmungsstörungen (AVWS)"] was developed by the German Society of Phoniatrics and Pediatric Audiology and standardized for school-age children. This study was designed to elucidate the validity of this questionnaire in preschool children. METHODS: The responses, which were given by the parents of 84 preschool children with respect to auditory discrimination and auditory memory, were correlated with the results of the Heidelberg screening test for preschool children (HVS), and their accuracy of prediction was determined. RESULTS: Similar to the results of other studies in school-age children, weak but significant correlations were found between the questionnaire results regarding auditory discrimination and auditory memory and the respective results of the HVS subtests. With a few exceptions, the questionnaire's accuracy of prediction was low. CONCLUSION: For preschool children, the questionnaire provides a reasonable method to get specific information about a child's history in a standardized and economic way. However, it is not valid as a screening or diagnostic tool.

[The influence of conductive hearing loss on DPOAE-threshold. The effect of an individually optimized stimulation]. / Der Einfluss einer Schallleitungsstörung auf die DPOAE-Schwelle. Möglichkeiten einer individuell optimierten Auslösung.

BACKGROUND: The DPOAE-threshold, estimated from extrapolated I/O functions, allows an objective assessment of the mechanical sensitivity of the inner ear. In children, the specificity of this diagnostic tool is impaired by conductive hearing loss. METHODS: In this study, we propose an individual optimization of the primary tone level ratio. This procedure allows the detection of a conductive hearing loss that can be accounted for when estimating the DPOAE-threshold. By means of a simulation using DPOAE-data from 22 normally hearing subjects, the effects of this procedure on the estimation of the DPOAE-threshold are examined. RESULTS: An individually optimized DPOAE stimulation distinctly improves the signal-to-noise ratio of the DPOAE which enables an estimation of the DPOAE-threshold for sound conductive losses up to 15 dB. The DPOAE-threshold only worsens in individual cases. CONCLUSIONS: An individually optimized stimulation paradigm may improve the specificity of inner ear diagnostics with the DPOAE-threshold. A clinical evaluation of the method in children, however, is necessary.

[Prosthetic voice rehabilitation after laryngectomy. Failures and complications after previous radiation therapy]. / Prothetische Stimmrehabilitation nach Laryngektomie. Komplikationen und Misserfolge nach vorheriger Bestrahlung.

BACKGROUND: Indwelling voice prostheses are state of the art for post-laryngectomy voice rehabilitation. The aim of this study was to identify the impact of radiation prior to tracheoesophageal puncture on success rate and complications. PATIENTS AND METHODS: We undertook a retrospective study of 145 patients who had undergone prosthetic voice restoration between 1990 and 2002 (Provox) and Provox2). Risks of functional failure and complications in 17 patients with previous radiation therapy were compared to those of 128 patients without such therapy. RESULTS: Previous radiation increased not only the risk of functional failure by 2.9 (P=0.023), but also the risk of shunt-related complications such as aspiration around the prosthesis (1.51; P=0.046), widening of the shunt (2.32; P=0.014), esophageal (2.51; P=0.013) or tracheal (3.29; P=0.0023) dislocation of the prosthesis and spontaneous (2.51; P=0.047) or surgical closure (3.76; P=0.037) of the shunt. CONCLUSION: Primary tracheoesophageal puncture during laryngectomy is recommended in cases without previous radiation therapy, especially when post-laryngectomy radiation is likely. In patients with previous radiation therapy, generally good success rates decrease, however, without absolute contraindication of tracheoesophageal puncture. These results may affect salvage surgery concepts.

[Speech impaired children. Anxiety, depression and quality of life of the mothers]. / Kinder mit Sprachentwicklungsauffälligkeiten. Angst, Depressivität und Lebensqualität der Mütter.

BACKGROUND: It is widely held that the well being of a mother significantly influences the way she brings up her child: Mothers with depression speak less to their child than healthy mothers do and so their emotional disorder has to be regarded an important cofactor for their child's speech development. On the other hand it is suspected that a mother's well being and quality of life may be influenced by her child especially in cases when the child suffers from impairment or developmental disturbance. As literature provides only little information on this topic the purpose of this study was to estimate both health related quality of life HRQOL and distinctive emotional reactions i.e. depression and anxiety in mothers of children with a speech developmental disorder. MATERIALS AND METHODS: 100 mothers (age 33.4+/-5.3 years, range: 22 to 47 years) of 100 preschool children (32 girls, 68 boys; age 4.2+/-1.5 years, range 1;3 to 7;7 years) with a speech impairment were investigated. Mothers of children with cochlear hearing loss, syndromes or other developmental disorders were excluded from the study. To estimate the prevalence of anxiety disorders and depression in the mothers the German version of the Hospital Anxiety and Depression Scale (HADS) was used. Data from 157 healthy women from the German test manual served as controls. HRQOL was assessed by the SF-36 questionnaire with age matched normal controls taken from the German test manual. Microsoft((R)) Excel and Matlab((R)) software packages were used for description, analysis, and evaluation. The differences in prevalence rates were tested by chi(2)-test and Wilcoxon's rank sum test. RESULTS: Assessed by the HADS-depression subscale 11% of the mothers of speech impaired children met criteria for depression compared to 2.5% in the control group. The prevalence in the study group was significantly higher ( p<0.01). The prevalence of anxiety disorders did not differ from normative data on a significant level ( p>5%). The SF-36 questionnaire revealed lower scores of most SF-36 subscales on different significance levels. The results of both tests correlated on a statistically significant level. CONCLUSIONS: Screening mothers of speech impaired children for a "soft" parameter like HRQOL and for epidemiologically relevant emotional disorders like depression and anxiety is of significant clinical interest. The SF-36 and the HADS are suitable tests. As the results of both tests are highly correlated for clinical purposes it seems reasonable to focus on depression and anxiety only. Up to now no data exist about how fathers of speech impaired children react emotionally, so this question has to be focused on in future. Although data allow no conclusion on whether the speech impairment is the reason or the consequence of a reduced HRQOL or an emotional disorder the results clearly indicate the necessity to take into account the mothers' well being when dealing with speech impaired children.

[Guidelines and their practical application in congenital hearing loss]. / Leitlinienumsetzung bei der Untersuchung und Behandlung permanent schwerhöriger Kinder.

BACKGROUND: Permanent congenital hearing loss in children does not only influence speech acquisition but also has a severe impact on the entire intellectual and psychological development, and thus social integration is handicapped. However, at least partial compensation can be achieved by complex rehabilitative measures. One of the first medical therapies in children with congenital hearing loss is to equip them with hearing aids. As part of quality management the purpose of this study is to discuss pedaudiological aspects and results of hearing - impaired children equipped with hearing aids against the background of guidelines from Germany and the US. METHODS: Data of 107 children equipped with hearing aids from 1997 to 1999 were analysed referring to the relevant German and US guideline. RESULTS: In 53 girls and 54 boys, 45% were suffering from at least severe, 45% from moderate and 10% from mild hearing loss. 93 children presented sensory hearing loss, 8 combined and 2 conductive hearing loss. 2 children had unilateral hearing loss, one a combined on one ear and a sensory hearing loss on the other and one child had a central auditory processing disorder. The age when the hearing loss was diagnosed depended on its grade and correlated with adverse environmental aspects. 34 children suffered from a syndrome or multiple handicaps, in these cases, the hearing loss was diagnosed at a later date than in children suffering from hearing loss only. In cases with near deafness audiological results with hearing aids were not sufficient; in these cases, cochlea implantation had to be discussed as an alternative measure. CONCLUSION: The data obtained from this study underline the need for universal hearing screening. Discussing the data against the relevant German and US guidelines clearly shows that German benchmarks are not as strict as the American ones. This has to be taken into account for further guideline development in Germany. As permanent hearing loss in children with syndromes and multiple handicaps and children with adverse environment is diagnosed at a later date than in other children public, measures have to be taken to improve this situation.

[Social orientation of parents of children with cleft lip and palate]. / Soziale Orientierung der Eltern von Kindern mit Lippen-Kiefer-Gaumen-Spalten.

BACKGROUND: Cleft lip and palate are the most common malformation in the orofacial region. The type and dimension of the cleft determine the functional limitations of respiration, swallowing, speech, articulation and hearing. In addition, cosmetic and communicative restrictions influence the cognitive, social and educational progress and the wellbeing of the children affected. Their parents face a difficult and lasting task: They have to cope with their child's handicap and the current standardised treatment procedures which start in early infancy. To guarantee optimum therapeutic success parents must be included as co-therapists. Therefore more information about parents' concerns and coping strategies are required. METHOD: To assess the strain put on parents of children with cleft lip and palate as well as the parents' coping strategies, a standardised questionnaire for the German-speaking parents was used during consultation in the out-patient clinic. RESULTS. In comparison with parents of children with other handicaps, the parents of children with cleft lip and palate feel less stressed out and adopt strategies of coping such as intensification of partnership, use of social support, as well as self-respect and fulfillment. Working mothers are less preoccupied and less at risk of being focussed on the handicapped child only. In comparison, the parents of children with Orofacial clefts focus less on the handicapped child in general than those parents whose children suffer from additional behavioural disorders. DISCUSSION: Though several functional, behavioural and psychological disorders may occur in children with cleft lip and palate their parents feel comparatively little stress. They do use a variety of coping strategies and tend to adopt a rather positive approach. Certainly, additional disorders of the child lead to more parental stress and likewise requiring more attention to the child which may even accentuate existing behavioural disorders. CONCLUSION: Parents of children with cleft lip and palate experience less stress in comparison with parents of children with other handicaps. Therapeutic efforts and regular check of the child's progress might support parents' coping strategies. Therapists should also ask for additional disorders such as behavioural disorders and initiate adequate support.

[Coping strategies in laryngectomy patients]. / Krankheitsbewältigungsstrategien laryngektomierter Patienten.

BACKGROUND: Over the last few years, paradigms for judging the results of treatment of tumor patients have shifted. In addition to characteristics such as the complete excision of the tumor and the duration of patient survival, restoring the quality of life has become an equally important aim. There is still a lack of systematic (and sufficient) research on coping strategies as a means of dealing with malignant tumors of the head and neck. PATIENTS AND METHOD: In a cross-sectional study, 25 laryngectomees, whose voices had been successfully restored with a Provox voice prosthesis,were examined for their coping strategies and the effects of the illness on their lives. The standardized Trier Scales of Coping Strategies and a custom-made questionnaire, which helped to structure the anamnesis of disease specific functional restrictions and the state of rehabilitation, were used as the means of inquiry. RESULTS: A high percentage of patients were content despite objective and subjective restrictions. Voice replacement was mainly experienced as unproblematic,with psychosocial restraints more commonly being felt in connection with pain and difficulties ingesting food. A correlation between the patients' evaluation of physical,psychological and social experiences and the coping strategies applied could not be verified. The way laryngectomees deal with their illness does not differ from the strategies of patients suffering from malignant or chronic diseases of other organ systems. CONCLUSION: The Trier Scales of Coping Strategies is a suitable means for determining the coping strategies of laryngectomees who have been successfully rehabilitated with the help of voice prostheses. The patients examined here did not apply different coping strategies from groups of patients with other severe illnesses. Obviously, the limitations on communication do not constitute a determining factor in coping with the disease. This finding is useful when planning psychological and social rehabilitation, e.g. by psychosomatic interventions.

Optimal L(1)-L(2) primary tone level separation remains independent of test frequency in humans.

Previous studies described a systematic asymmetry of the level of the 2f(1)-f(2) distortion product otoacoustic emission (DP) in the space of the primary tones levels L(1) and L(2) in normal-hearing humans. Optimal primary tone level separations L(1)-L(2), which result in maximum DP levels, were close to L(1)=L(2) at high levels, but continuously increased with decreasing stimulus level towards L(1)>L(2) (Gaskill and Brown, 1990, J. Acoust. Soc. Am. 88, 821-839). At these optimal L(1)-L(2), however, not only DP levels in normal hearing were maximal, but also trauma-induced DP reductions. A linear equation that approximates optimal L(1)-L(2) level separations thus was suggested to be optimum for use in clinical applications (Whitehead et al., 1995, J. Acoust. Soc. Am. 97, 2359-2377). It was the aim of this study to extend the generality of optimal L(1)-L(2) separations to the typical human test frequency range for f(2) frequencies between 1 and 8 kHz. DPs were measured in 22 normal-hearing human ears at 61 primary tone level combinations, with L(2) between 5 and 65 dB SPL and L(1) between 30 and 70 dB SPL (f(2)/f(1)=1.2). It was found that the systematic dependence of the maximum DP level on the L(1)-L(2) separation is independent on frequency. Optimal L(1)-L(2) level separations may well be approximated by a linear equation L(1)=a L(2)+(1-a) b (after Whitehead et al., 1995) with parameters a=0.4 and b=70 dB SPL at f(2) frequencies between 1 and 8 kHz and L(2) levels between 20 and 65 dB SPL. Below L(2)=20 dB SPL, the optimal L(1) was found to be almost constant. Following previous notions (Gaskill and Brown, 1990), an analysis of basilar membrane response data in experimental animals (after Ruggero and Rich, 1991, Hear. Res. 51, 215-230) is further presented that relates optimal L(1)-L(2) separations to frequency-selective compression of the basilar membrane. Based on the assumption that optimal conditions for the DP generation are equal primary tone responses at the f(2) place, a linear increase of the optimal L(1)-L(2) level separation is graphically demonstrated, similar to our results in human ears.

[Assessment of outer hair cell function recovery by means of the DPOAE threshold]. / Die Erfassung von Regenerationsvorgängen äusserer Haarzellen mit Hilfe der DPOAE-Schwelle.

Distortion product otoacoustic emissions (DPOAE) originate from nonlinear mechanical sound processing in the inner ear, mainly due to normal outer hair cell function. Outer hair cell impairment can be detected by means of DPOAE. With a special primary tone level paradigm which optimises the primary tone level difference over a wide stimulus level range (L1 = 0.4 L2 + 39 dB, L2 = 20 to 65 dB SPL, f2 = 0.5 to 8 kHz, f2/f1 = 1.2), DPOAE can be measured at levels close to the psychophysical hearing threshold. From the DPOAE growth functions, which are constructed from measurements at different stimulus levels, a DPOAE threshold can be defined (Boege et al., 1998), which can be interpreted as a threshold of mechanical processing by the outer hair cells. In this study, DPOAE thresholds were examined in 9 patients with reversible cochlear hearing loss, i.e. sudden deafness or noise trauma. With increasing hearing loss, low primary tone level DPOAE in particular decreased, and thus the DPOAE threshold increased. The DPOAE threshold makes it possible to detect mechanical sensitivity losses in a frequency-specific manner. Thus, loss of mechanical amplification may be differentiated from a non-mechanical cause of hearing loss.

Growth behavior of the 2 f1-f2 distortion product otoacoustic emission in tinnitus.

High-resolution hearing threshold and 2 f1-f2 distortion product otoacoustic emission (DP) were measured with the same in-the-ear sound probe and same calibration at 51 frequencies between 500 and 8000 Hz in 39 sensorineural hearing loss ears associated with tinnitus. Using a primary tone setting L1 = 0.4L2 + 39 that accounts for the nonlinear interaction of the two primary tones at the DP generation site at f2, DPs were elicited in a wide range from L2 = 65 to 20 dB SPL. We failed to find a uniform DP behavior in the 39 tinnitus ears tested. Seventeen of them behaved like impaired ears without tinnitus. In these ears a linearized DP growth was observed where the DP level decreased and the slope of the DP I/O functions steepened with increasing hearing loss and as a result both the DP level and the DP slope strongly correlated with hearing threshold. The other population, 22 tinnitus ears, exhibited a poor or even inverse relationship between DP level and hearing threshold, i.e., displayed an increase of DP level with increasing hearing loss. Despite the severe hearing loss but due to the high level, DPs could be recorded well in the frequency range that corresponded to the appearance of the tinnitus. The DP slope, however, increased with increasing hearing loss and, therefore, did still correlate with hearing threshold revealing pathological alteration. The data suggest that the DP level alone is hardly capable of assessing hearing impairment in tinnitus ears and may even be misleading. Thus just the DP slope seems to be the only reliable indicator of cochlear malfunction around the tinnitus frequency. The observed nonuniform DP behavior suggests different cochlear impairments in tinnitus ears. In those ears where the DP level decreases and the slope of the I/O functions increases with hearing loss, cochlear sensitivity and tuning are supposed to be diminished. In those ears where the DP level increases with increasing hearing loss, a reinforced mechanical distortion is hypothetized to be generated by cochlear hyperactivity that can be the source of both the abnormally high DP level and the tinnitus.

The level and growth behavior of the 2 f1-f2 distortion product otoacoustic emission and its relationship to auditory sensitivity in normal hearing and cochlear hearing loss.

The 2 f1-f2 distortion product otoacoustic emission (DP) was measured in 20 normal hearing subjects and 15 patients with moderate cochlear hearing loss and compared to the pure-tone hearing threshold, measured with the same probe system at the f2 frequencies. DPs were elicited over a wide primary tone level range between L2 = 20 and 65 dB SPL. With decreasing L2, the L1-L2 primary tone level difference was continuously increased according to L1 = 0.4L2 + 39 dB, to account for differences of the primary tone responses at the f2 place. Above 1.5 kHz, DPs were measurable with that paradigm on average within 10 dB of the average hearing threshold in both subject groups. The growth of the DP was compressive in normal hearing subjects, with strong saturation at moderate primary tone levels. In cases of cochlear impairment, reductions of the DP level were greatest at lowest, but smallest at highest stimulus levels, such that the growth of the DP became linearized. The correlation of the DP level to the hearing threshold was found to depend on the stimulus level. Maximal correlations were found in impaired ears at moderate primary tone levels around L2 = 45 dB SPL, but at lowest stimulus levels in normal hearing (L2 = 25 dB SPL). At these levels, 17/20 impaired ears and 14/15 normally hearing ears showed statistically significant correlations. It is concluded that for a clinical application and prediction of the hearing threshold, DPs should be measured not only at high, but also at lower primary tone levels.

Suppression tuning characteristics of the 2 f1-f2 distortion-product otoacoustic emission in humans.

The suppression tuning properties of the 2 f1-f2 distortion-product otoacoustic emission (DPOAE) were measured in 16 ears of normally hearing human subjects. DPOAE were elicited by fixed, low-level primary tones in four frequency regions with the second primary tone frequency f2 at 1, 2, 4, and 6 kHz. For various suppressor frequencies, suppression of the DPOAE was measured as a function of the suppressor tone level, enabling the assessment of the threshold and the growth of suppression. Depending on the distance of the suppressor tone to f2, there were marked differences in the suppression behavior of different suppressor frequencies. The threshold of suppression was minimal slightly above f2 and hardly increased with increasing frequency, but increased continuously with decreasing suppressor frequency. The growth of suppression, however, did not systematically change below f2, but decreased rapidly above f2. Both changes resulted in asymmetrical, V-shaped suppression tuning curves. They were sharply tuned to a frequency slightly above f2, with Q10 dB values up to 7.87. This is consistent with the assumption that the main source of the DPOAE is at the f2 site. In some cases, the DPOAE was particularly sensitive to suppressor tones near the DPOAE frequency. In one individual case, facilitation was found for corresponding frequency-level ranges of the suppressor tone. This may suggest a secondary emission source at the distortion product place.

Monoamine metabolites in the CSF of conscious unrestrained cats.

The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured repeatedly over a period of up to 5 months at different sites of the brain ventricular system in unrestrained, awake cats. Samples of 10 microliter CSF were analyzed by high pressure liquid chromatography and subsequent electrochemical detection. Concentrations were in the range of 30-130 ng/ml for DOPAC, 110-340 ng/ml for 5-HIAA and 180-750 ng/ml for HVA. The monoamine metabolites were constant even over a period of several months if measured in the same animal but there was a marked interindividual variation. A marked gradient for monoamine metabolites was found when CSF samples from frontal sites of the lateral ventricle were compared to CSF samples from the dorsal lateral ventricle. The concentrations of DOPAC and HVA were higher at frontal sites.

Involvement of dopamine in amygdaloid kindling.

The concentrations of dopamine, noradrenaline, and dihydroxyphenylacetic acid were determined in the amygdala, neostriatum, neocortex, hippocampus, brain stem, and hypothalamus of cats, which had had 9 to 14 tonic-clonic kindled seizures. No significant biochemical changes were observed compared to control cats. Pharmacological manipulations of dopamine receptors (haloperidol, apomorphine) did not modify the kindling procedure. According to the data it seems unlikely that dopamine plays a major role in amygdaloid kindling.

Long-term application of haloperidol: effects on dopamine and acetylcholine receptors.

Rats were injected daily with haloperidol, 0.5 mg/kg i.p., or pimozide, 2 mg/kg i.p., for a period of 8 or 16 days, respectively. 24 h after the last injection of haloperidol, these rats were challenged with gamma-butyrolactone (GBL) in doses of 200-750 mg/kg i.p. In haloperidol-treated rats, higher doses of GBL are needed in order to increase the rate of dopa accumulation. This finding demonstrates the development of supersensitivity of dopamine (DA) autoreceptors towards endogenously released DA. Pimozide had no effect on the increased rate of dopa accumulation induced by increasing doses of GBL. From this data it is concluded that pimozide in our model is mainly active on postsynaptic DA receptors and haloperidol is active on pre- and postsynaptic DA receptors. In rats treated chronically with daily injections of haloperidol, benztropine, in a dose of 50 mg/kg, induced a decrease in dopa accumulation which was more marked than the decrease seen with benztropine, 50 mg/kg in animals treated with a single injection of haloperidol only. The opiate antagonist, naloxone at a dose of 10 mg/kg, had no effect on these results. Benztropine, 50 mg/kg i.p., had no effect on the increased rate of dopa accumulation induced by GBL, 400 mg/kg. The data support the hypothesis that in parallel to the development of supersensitive postsynaptic DA receptors, there is a development of subsensitivity in cholinergic receptors within the nigro-neostriatal system. Further the results show that a new DA-acetylcholine equilibrium is reached during long-term haloperidol treatment. The implications of these findings in regard to extrapyramidal side effects during long-term neuroleptic treatment are briefly discussed.

Supersensitivity of dopamine-autoreceptors. The effect of gammabutyrolactone in long-term haloperidol treated rats.

Rats were injected daily with haloperidol, 0.5 mg/kg i.p. for a period of 16 days. 24 hours after the last injection of haloperidol these rats were challenged with gammabutyrolactone in doses of 200-750 mg/kg i.p. The ensuing increase in neostriatal dopa-accumulation was significantly lower than in rats not previously treated with haloperidol. Since the increase in dopa-accumulation following GBL-treatment is most probably independent of postsynaptically located DA-receptors the difference between the experimental series is explained in terms of reduced feedback activation of DA-synthesis due to the increased sensitivity of presynaptically located DA-autoreceptors.