A healthy 29-year-old woman received epidural block for severe lumbago in an outpatient clinic. Fifteen minutes after injection of mepivacaine 0.5% with dexamethasone into the epidural space, the patient complained of itching of eyelids followed by generalized pruritus. Hypotension, erythema and generalized urticaria were observed. Initial treatment was with 100% oxygen through face mask, and additional intravenous fluids, followed by administration of adrenaline, chlorpheniramine and dopamine. Cardiac ultrasound examination showed mildly impaired movement of inferior to septal wall. Her plasma histamine level was transiently elevated during the anaphylactic event; however the serum tryptase level was not. Biological assays for confirming the causative agent and cutaneous test were all negative, but clinical symptoms positivity showed nonimmunological anaphylactic reaction to mepivacaine or dexamethasone. This case report confirms the need for systematic allergological investigation in a case of immediate hypersensitivity reaction occurring during nerve block in patients who had even received similar nerve blocks repeatedly. Pain clinician should be aware of the possibility of anaphylactic reactions involving any drug or substance used for an outpatient.

Dystonia is an involuntary movement disorder characterized by repetitive patterned or sustained muscle contractions causing twisting or abnormal postures. Several lines of evidence suggest that abnormalities of dopaminergic pathways contribute to the pathophysiology of dystonia. In particular, dysfunction of D2-like receptors that mediate function of the indirect pathway in the basal ganglia may play a key role. We have demonstrated with positron emission tomography that patients with primary focal cranial or hand dystonia have reduced putamenal specific binding of [(18)F]spiperone, a nonselective D2-like radioligand with nearly equal affinity for serotonergic 5-HT(2A) sites. We then repeated the study with [(18)F]N-methyl-benperidol (NMB), a more selective D2-like receptor radioligand with minimal affinity for 5-HT(2A). Surprisingly, there was no decrease in NMB binding in the putamen of subjects with dystonia. Our findings excluded reductions of putamenal uptake greater than 20% with 95% confidence intervals. The analysis of the in vitro selectivity of NMB and spiperone demonstrated that NMB was highly selective for D2 receptors relative to D3 receptors (200-fold difference in affinity), whereas spiperone has similar affinity for all three of the D2-like receptor subtypes. These findings when coupled with other literature suggest that a defect in D3, rather than D2, receptor expression may be associated with primary focal dystonia. © 2010 Movement Disorder Society.

Animal studies have shown dopamine transporter protein (DAT1) knock out mice are growth retarded and hyperactive. DAT1 has been researched in several human psychiatric studies with varying results regarding phenotype and DAT1 alleles. However, the relationship between DAT1 and short stature in humans has not been explored. Buccal swabs were collected from patients receiving growth hormone (GH) therapy and were genotyped for variable number tandem repeat (VNTR) by polymerase chain reaction. Forty subjects were included; twenty-three patients had the 10/10 DAT1 genotype and thirteen had the 9/10 genotype. Fifteen of the patients with the 10/10 genotype tested GH deficient. Seven patients with the 9/10 genotype tested GH sufficient. The linear growth rate during the first year of GH therapy was equivalent in both genotypes. In conclusion, polymorphisms in the DAT1 40 base pair (bp) VNTR genotype do not predict GH deficiency or response to GH therapy in short children.

The prolactin regulatory element-binding protein (PREB) is a transcription factor that regulates prolactin (PRL) promoter activity in the rat anterior pituitary. PRL gene expression and secretion are regulated by various hormones and growth factors, including dopamine, epidermal growth factor, and thyrotropin-releasing hormone (TRH). We examined the effect of TRH on PREB expression in pituitary cells. Western blots probed with a PREB-specific antiserum showed that the relative abundance of PREB in GH3 cells increased on treatment with TRH in a dose-dependent manner. The relative abundance of PREB mRNA also increased in a dose-dependent manner after treatment with TRH. TRH induced the expression of the luciferase reporter protein under the PREB promoter control. We used inhibitors of certain signal transduction pathways to show that TRH-induced PREB induction is sensitive to the protein kinase A (PKA) inhibitor. TRH stimulated the activity of the wild-type PRL promoter, whereas mutation of the PREB core-binding element on the PRL promoter reduced this ability. In summary, we have shown that TRH stimulated PREB expression in GH3 cells via the PKA pathway. PREB can function as a transcriptional regulator of PRL promoter activity and might be involved in TRH-induced PRL gene transcription.

Fugitive acromegaly is most commonly caused by pituitary acidophil stem cell adenomas, and is characterized by a relatively short clinical history, a large and locally invasive tumor, and relatively low hormonal activity. Here, we report an unusual case of fugitive acromegaly that initially presented as invasive prolactinoma. A 48-year-old man with a huge pituitary mass extending to the suprasellar area was referred to our hospital in December 2007. He had undergone transsphenoidal surgery in November 1999 because of a large invasive prolactinoma. The tumor had grown progressively, despite therapy with dopamine agonists. Subtle features of acromegaly were noted and serum IGF-1 levels were high (733 ng/ml). An oral glucose tolerance test revealed that basal and nadir levels of growth hormone (GH) were 1.56 and 1 ng/ml, respectively. As a therapeutic trial, long-acting octreotide (20 mg IM, monthly) was added, and the tumor size markedly reduced within 6 months on magnetic resonance imaging examination. Immunohistochemical staining of the tumor tissue obtained at the surgery in 1999 showed positive staining for GH and prolactin (PRL). Double immunofluorescence staining showed a mixed positivity for GH and PRL in the majority of tumor cells; however, the two hormones colocalized in a minority of tumor cells, indicating that the tumor was composed of three different cell types (GH, PRL, and GH/PRL). The diagnosis of fugitive acromegaly was initially overlooked in this patient because of normal serum GH levels and a lack of acromegalic features, although histological evidence for GH production was present. IGF-1 determinations would be helpful for the diagnosis of fugitive acromegaly.

RATIONALE: In utero cocaine exposure has been associated with alterations in the dopamine (DA) system in monkeys. However, the behavioral outcomes of prenatal cocaine exposure in adulthood are poorly understood.

OBJECTIVES: To assess several behavioral measures in 14-year-old rhesus monkeys exposed to cocaine in utero and controls (n?=?10 per group).

MATERIALS AND METHODS: For these studies, two unconditioned behavioral tasks, novel object reactivity and locomotor activity, and two conditioned behavioral tasks, response extinction and delay discounting, were examined. In addition, cerebrospinal fluid (CSF) samples were analyzed for concentrations of the monoamine metabolites homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA).

RESULTS: No differences in CSF concentrations of 5-HIAA and HVA, latencies to touch a novel object or locomotor activity measures were observed between groups or sexes. However, prenatally cocaine-exposed monkeys required a significantly greater number of sessions to reach criteria for extinction of food-reinforced behavior than control monkeys. On the delay-discounting task, male prenatally cocaine-exposed monkeys switched preference from the larger reinforcer to the smaller one at shorter delay values than male control monkeys; no differences were observed in females.

CONCLUSIONS: These findings suggest that prenatal cocaine exposure results in long-term neurobehavioral deficits that are influenced by sex of the individual.

RATIONALE: It is known that dopaminergic cell loss leads to increased endogenous cannabinoid levels and CB1 receptor density.

OBJECTIVE: The aim of this study was to evaluate the influence of dopaminergic cell loss, induced by injection of 6-hydroxydopamine, on the effects exerted by cannabinoid agonists on neuron activity in the subthalamic nucleus (STN) of anesthetized rats.

RESULTS: We have previously shown that ?(9)-tetrahydrocannabinol (?(9)-THC) and anandamide induce both stimulation and inhibition of STN neuron activity and that endocannabinoids mediate tonic control of STN activity. Here, we show that in intact rats, the cannabinoid agonist WIN 55,212-2 stimulated all recorded STN neurons. Conversely, after dopaminergic depletion, WIN 55,212-2, ?(9)-THC, or anandamide inhibited the STN firing rate without altering its discharge pattern, and stimulatory effects were not observed. Moreover, anandamide exerted a more intense inhibitory effect in lesioned rats in comparison to control rats.

CONCLUSIONS: Cannabinoids induce different effects on the STN depending on the integrity of the nigrostriatal pathway. These findings advance our understanding of the role of cannabinoids in diseases involving dopamine deficits.

Background:? The anatomical proximity of the cannabinoid type 1 (CNR1/CB1R) and the dopamine D2 receptors (DRD2), their ability to form CB1R-DRD2 heteromers, their opposing roles in locomotion, and their involvement in ethanol’s reinforcing and addictive properties prompted us to study the levels and distribution of CB1R after chronic ethanol intake, in the presence and absence of DRD2. Methods:? We monitored the drinking patterns and locomotor activity of Drd2+/+ and Drd2-/- mice consuming either water or a 20% (v/v) ethanol solution (forced ethanol intake) for 6?months and used the selective CB1 receptor antagonist [(3) H]SR141716A to quantify CB1R levels in different brain regions with in vitro receptor autoradiography. Results:? We found that the lack of DRD2 leads to a marked upregulation (approximately 2-fold increase) of CB1R in the cerebral cortex, the caudate-putamen, and the nucleus accumbens, which was reversed by chronic ethanol intake. Conclusions:? The results suggest that DRD2-mediated dopaminergic neurotransmission and chronic ethanol intake exert an inhibitory effect on cannabinoid receptor expression in cortical and striatal regions implicated in the reinforcing and addictive properties of ethanol.

Copyright © 2010 by the Research Society on Alcoholism.

Background and purpose: We have previously reported that galantamine, a weak acetylcholinesterase inhibitor, improves prepulse inhibition (PPI) deficits in mice reared in social isolation. ACh receptors are involved in the underlying mechanism of PPI, but whether rearing in social isolation causes dysfunction of the cholinergic system is unknown. In this study we examined the involvement of muscarinic receptors in the improvement of PPI deficits induced by galantamine, and whether the cholinergic system is altered in mice reared in isolation. Experimental approach: Three-week-old male ddY mice were housed in isolated cages for 6 weeks before the initiation of experiments to create PPI deficits. Cholinergic functions were determined by measuring the behavioural and neurochemical responses to nicotinic and muscarinic receptor agonists. Key results: The improvement by galantamine of social isolation-induced PPI deficits was blocked by scopolamine, a non-selective muscarinic antagonist, and telenzepine, a preferential M(1) receptor antagonist. Activation of M(1) receptors improved social isolation-induced PPI deficits. Social isolation did not affect choline acetyltransferase and acetylcholinesterase activities in the prefrontal cortex and hippocampus, but it reduced the locomotor-suppressive response to muscarinic agonist oxotremorine, but not to nicotine. The isolation also attenuated the M(1) receptor agonist N-desmethylclozapine-induced increase in prefrontal dopamine release. Conclusions and implications: Galantamine improves PPI deficits of mice reared in social isolation via activation of M(1) receptors. Social isolation reduces the muscarinic, especially M(1) , receptor function and this is involved in PPI deficits.

© 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.