Search results for "PAM"
showing 10 items of 1768 documents
Pharmacological heterogeneity of γ-aminobutyric acid receptors during development suggests distinct classes of rat cerebellar granule cells in situ
2001
The gamma-aminobutyric acid receptor (GABA(A)R) represents a ligand-gated Cl(-)-channel assembling as heteropentamere from 19 known subunits. Cerebellar granule cells contain a unique subset, namely the alpha1-, alpha6-, beta2-, gamma2- and delta-subunits. We studied their GABAergic pharmacology in situ using whole-cell patch-clamp recordings in brain slices and a modified Y-tube application system. The distribution of the EC50s for GABA in young (P8-P14) and medium aged animals (P15-P28) could be fitted with the sum of two Gaussian distributions with means of 60 and 185 microM and 27 and 214 microM, respectively. In older animals (P29-P48) the observed homogeneous range of sensitivities fi…
Pain perception in Parkinson's disease: A systematic review and meta-analysis of experimental studies
2017
While hyperalgesia (increased pain sensitivity) has been suggested to contribute to the increased prevalence of clinical pain in Parkinson's disease (PD), experimental research is equivocal and mechanisms are poorly understood. We conducted a meta-analysis of studies comparing PD patients to healthy controls (HCs) in their response to experimental pain stimuli. Articles were acquired through systematic searches of major databases from inception until 10/2016. Twenty-six studies met inclusion criteria, comprising 1292 participants (PD = 739, HCs = 553). Random effects meta-analysis of standardized mean differences (SMD) revealed lower pain threshold (indicating hyperalgesia) in PD patients d…
Opiate-induced dopamine release is modulated by severity of alcohol dependence: an [(18)F]fallypride positron emission tomography study.
2011
Background Preclinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain. Specifically, alcohol-induced release of β-endorphins stimulates μ-opioid receptors (MORs), which is believed to cause dopamine release in the brain reward system. Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol. In the present study, a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effect…
GnRH agonist versus recombinant HCG in an oocyte donation programme: a randomized, prospective, controlled, assessor-blind study.
2009
The use of gonadotrophin-releasing hormone (GnRH) agonists for triggering ovulation remains controversial. The primary objective of this study was to evaluate the incidence of ovarian hyperstimulation syndrome (OHSS) following GnRH agonist versus recombinant human chorionic gonadotrophin (HCG) as methods for triggering ovulation. A second aim was to compare the clinical outcome and embryo quality according to the two procedures. The cycle characteristics of 100 oocyte donors undergoing ovarian stimulation and IVF outcomes of their 100 oocyte recipients were analysed. Donors were prospectively randomized into two groups on the last day of ovarian stimulation: Group I received a single bolus …
Dopaminergic modulation of low-Mg2+-induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro
2012
To investigate whether epileptiform activity in the immature brain is modulated by dopamine, we examined the effects of dopaminergic agonists and antagonists in an intact in vitro preparation of the isolated corticohippocampal formation of immature (postnatal days 3 and 4) C57/Bl6 mice using field potential recordings from CA3. Epileptiform discharges were induced by a reduction of the extracellular Mg(2+) concentration to 0.2 mM. These experiments revealed that low concentrations of dopamine ( 3 μM dopamine enhanced epileptiform activity. The D1-agonist SKF38393 (10 μM) had a strong proconvulsive effect, and the D2-like agonist quinpirole (10 μM) mediated a weak anticonvulsive effect. The …
Synthesis and Characterization of a Novel Series of Agonist Compounds as Potential Radiopharmaceuticals for Imaging Dopamine D-2/3 Receptors in Their…
2014
Imaging of dopamine D2/3 receptors (D2/3R) can shed light on the nature of several neuropsychiatric disorders in which dysregulation of D2/3R signaling is involved. Agonist D2/3 tracers for PET/SPECT imaging are considered to be superior to antagonists because they are more sensitive to dopamine concentrations and may selectively label the high-affinity receptor state. Carbon-11-labeled D2/3R agonists have been developed, but these short-lived tracers can be used only in centers with a cyclotron. Here, we report the development of a series of novel D2R agonist compounds based on the 2-aminomethylchromane (AMC) scaffold that provides ample opportunities for the introduction of longer-lived […
Locomotor and antidepressant-like effects of 5-HT(1A) agonist LY 228729 in prenatally benzodiazepine-exposed rats.
1998
Locomotor activity and antidepressant-like effect in the forced swim test (FST) of 5-HT(1A) agonist LY 228729 were investigated in adult rats prenatally exposed at doses of diazepam (DZ) and alprazolam (ALP) which induce persistent downregulation of GABA/ benzodiazepine (BZ) receptors. Prenatal exposure to ALP and DZ did not modify the efficacy of subchronic LY 228729 to decrease immobility time in the FST. Prenatal DZ and ALP potentiated the facilitatory effect of subchronic LY 228729 on locomotor activity; prenatal DZ was more effective than prenatal ALP. Moreover, prenatal DZ increased stereotypic movements induced by LY 228729. These data suggest that the persistent downregulation of GA…
New dopamine D2 receptor polymorphisms in rats and association with apomorphine-induced stereotypies.
2002
Adult Wistar rats injected with the dopamine receptor agonist apomorphine display different types of motility patterns with respect to oral stereotypes and locomotor activities. It was tested whether phenotypes exhibiting either ‘sniffing’ or ‘non-sniffing’ behaviour differed in gene structures of dopamine receptors D1 or D2. Forty-five Wistar rats of both genders were tested after a single dose of apomorphine (2 mg/kg s.c.) for stereotyped behaviour. Sequence analysis of the 5′ flanking region, the 5′ untranslated region and the coding region of the two genes revealed a new sequence for the 5′ flanking region of the D1 receptor gene and two polymorphisms in the promoter region of the D2 re…
Anxiolytic-like effects of acute and chronic GABA transporter inhibition in rats.
2002
Acute GABA transporter inhibition can induce anxiolytic-like behaviors. The present analysis addressed whether chronic treatment (23 days via drinking water) with a GABA transporter inhibitor affects rat behavior similar to acute treatment and interferes with additional benzodiazepine-receptor agonistic treatment. Seventy-one rats divided into seven groups were acutely treated with either vehicle, diazepam (2 mg/kg), zolpidem (0.05 mg/kg), tiagabine (19 mg/kg) or chronically with tiagabine with or without acute diazepam or zolpidem. Animals were behaviorally characterized in an elevated plus-maze. None of the treatments induced changes in the activity of the animals. Acute and chronic treat…
The 5-HT and alpha-adrenoceptor antagonist effect of four benzylisoquinoline alkaloids on rat aorta.
1998
Abstract The action of four benzylisoquinoline alkaloids (two aporphines—glaucine and apomorphine, a benzylisoquinoline—papaverine and a bisbenzyltetrahydroisoquinoline—antioquine) on 5-HT-induced contraction in rat thoracic aorta has been examined and compared with that of the control drugs: ketanserin, nifedipine, prazosin and phentolamine. The relaxant action on 5-HT-induced contraction was contrasted with that on the contraction induced by noradrenaline and KCl. The results obtained with control drugs show that ketanserin has clear selectivity for 5-HT receptors, whereas prazosin and phentolamine have high selectivity for the α1-adrenoceptor and nifedipine seems to have a more potent ef…