The postnatal maturation of dopamine innervation in the prefrontal cortex of gerbils (Meriones unguiculatus) is sensitive to an early single dose of methamphetamine. A quantitative immunocytochemical study.

Dawirs RR, Teuchert-Noodt G, Czaniera R. The postnatal maturation of dopamine innervation in the prefrontal cortex of gerbils (Meriones unguiculatus) is sensitive to an early single dose of methamphetamine. A quantitative immunocytochemical study. J Hirnforsch. 1994;35(2):195-204.Dopamine (DA)-immunoreactivity was investigated in the prefrontal cortex (PFC) of 90 day old adult male gerbils (Meriones unguiculatus) after they had received a single dose of either methamphetamine (50 mg/kg; i.p.) or saline at the age of postnatal day 14. For that purpose, a selective and sensitive antibody directed against glutaraldehyde-conjugated dopamine was applied. All detectable fragments of dopamine-immunoreactive fibres were identified in consecutive frontal sections of the pregenual prefrontal cortex, and their total numbers and total length were determined in the medial (mPFC) and orbital prefrontal cortex (oPFC). The results indicate that a single application of methamphetamine during early postnatal development caused a significant and severe restraint of the subsequent maturation of the prefrontal dopamine-innervation. Although, on postnatal day 14, the total dopamine-immunoreactivity had only attained about 4% (mPFC) and 7% (oPFC) of the regular adult values, this solitary pharmacological challenge entailed final adult innervation densities which were about 38% (mPFC) and 50% (oPFC) below those of the controls. Considering the pivotal role which mesoprefrontal dopaminergic afferents play in morphogenesis and regular functioning, the present results are discussed with current understanding of structural and functional plasticity during maturation of the prefrontal cortex

Maturation of the dopamine innervation during postnatal development of the prefrontal cortex in gerbils (Meriones unguiculatus). A quantitative immunocytochemical study.

Dawirs RR, Teuchert-Noodt G, Czaniera R. Maturation of the dopamine innervation during postnatal development of the prefrontal cortex in gerbils (Meriones unguiculatus). A quantitative immunocytochemical study. J Hirnforsch. 1993;34(3):281-290.Dopamine (DA)-immunoreactivity was investigated in the prefrontal cortex of gerbils (Meriones unguiculatus). For that purpose, a sensitive and selective antibody against glutaraldehyde-conjugated dopamine was applied. All detectable fragments of dopamine-immunoreactive nerve fibres were identified in selected consecutive frontal sections and their total length was determined in both the medial and orbital prefrontal cortex on postnatal days 7, 14, 23, 30, 60, and 90. Dopamine immunoreactivity revealed exponential growth until postnatal day 30, and further increased until postnatal day 90 with reduced increments. Due to higher initial percentage growth rates the dopamine innervation in the orbital prefrontal cortex achieved maturity earlier than in the medial prefrontal areas. Quantitative maturation of the prefrontal DA innervation is discussed with current data on functional and structural development of the prefrontal cortex

Ontogeny of PFC-related behaviours is sensitive to a single non-invasive dose of methamphetamine in neonatal gerbils (Meriones unguiculatus).

Dawirs RR, Teuchert-Noodt G, Czaniera R. Ontogeny of PFC-related behaviours is sensitive to a single non-invasive dose of methamphetamine in neonatal gerbils (Meriones unguiculatus). J Neural Transm. 1996;103(11):1235-1245.A single dose of methamphetamine (50 mg/kg; i.p.) was administered to neonatal male gerbils (Meriones unguiculatus) aged 14 days, and adult prefrontal cortex (PFC)-related behaviours were analysed and compared with saline-treated controls at the age of postnatal day 90. For that purpose, animals were tested for open-field activities and y-maze delayed alternation. This solitary and non-invasive drug challenge, which has recently been found to initiate serious restraint in maturation of the mesoprefrontal dopamine (DA)-system (Dawirs et al., 1994), induces a significant delayed alternation impairment as well as significant increases in open-field motor activity and emotionality. Since an undisturbed development of the prefrontal DA-innervation seems to be a precondition for the maturation of normal PFC-related behaviours, a single early methamphetamine impact may be a suitable animal model for further investigation of structural and functional aspects of non-invasively induced behavioural deficits in rodents. The present results are discussed with regard to the assumption that hypofunctional mesoprefrontal DA-systems might be basic to schizophrenic behaviours in man

Burden and attitude to resistant and refractory migraine: a survey from the European Headache Federation with the endorsement of the European Migraine & Headache Alliance

Background: New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to-treat migraine patients in a standardized way. The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportunities) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts). The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions. Methods: We conducted a web-questionnaire-based cross-sectional international study involving physicians with interest in headache care. Results: There were 277 questionnaires available for analysis. A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resistant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively). However, many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week. Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care. Conclusions: This report highlights the clinical relevance of difficult-to-treat migraine and the presence of unmet needs in this field. There is the need of more evidence regarding the management of those patients and clear guidance referring to the organization of care and available opportunities