Mice lacking dopamine D1 receptors express normal lithium chloride-induced conditioned taste aversion for salt but not sucrose

Conditioned taste aversion (CTA), is a form of Pavlovian learning wherein a novel flavour is powerfully associated with subsequent feelings of illness, and is afterwards avoided. In rats, pharmacological blockade of dopamine D1 receptors has been reported to prevent the expression of a CTA to the sweet taste of sucrose or saccharine. We used genetically modified mice to determine whether dopamine D1 receptors are necessary for the expression of a CTA. Food-deprived mice lacking the dopamine D1 receptor (D1r-/-) did not express a LiCl-induced (125 or 254 mg/kg) CTA to the sweet taste of 0.5 m sucrose, in agreement with previous pharmacological studies. However, water-deprived D1r-/- mice did express normal LiCl-induced (40, 150 and 254 mg/kg) CTA to a salty taste (0.2 m NaCl). Our results suggest that activation of D1 receptors might contribute to the strength of an aversive gustatory association, but might not be required for the formation of a CTA in general.     

Involvement of rostral prefrontal cortex in selection between stimulus-oriented and stimulus-independent thought

We used functional magnetic resonance imaging to investigate brain activity while healthy subjects performed three different tasks, each of which alternated between: (i) phases relying on stimulus-oriented thought (i.e. cognitive processes provoked by incoming sensory information); and (ii) phases relying on stimulus-independent thought (i.e. cognitive processes that were not related to any information in the immediate sensory environment). Within each task, the two phases were matched as closely as possible. In all three tasks, lateral rostral prefrontal cortex was transiently activated by a switch between stimulus-oriented and stimulus-independent thought (regardless of the direction of the switch). Medial rostral prefrontal cortex consistently exhibited sustained activity for stimulus-oriented vs. stimulus-independent thought. These results suggest the involvement of rostral prefrontal cortex in selection between stimulus-oriented and stimulus-independent cognitive processes.     

Selective and persistent effect of foetal sex on cognition in pregnant women

Despite widespread anecdotal complaints of impairment, systematic research addressing cognition in gestating women has yielded equivocal results. One way that ambiguous findings could arise is if male and female foetuses affect maternal cognition in different ways. Using a longitudinal within-participants design, we tracked women's cognitive performance from early pregnancy through to postnatal resumption of menstruation. On several cognitive tests, the sex of the foetus was unrelated to maternal performance. But specifically on difficult tests of working memory and spatial ability, a large and enduring effect of foetal sex was evident: women pregnant with boys consistently outperformed women pregnant with girls. A foetal-derived factor that differs in type or concentration between male and female foetuses may thus influence mothers' cognition.     

Recent advances in Parkinson's disease therapy: use of monoamine oxidase inhibitors

Monoamine oxidase inhibitors inhibit dopamine metabolism and are therefore effective in treating Parkinson's disease, a condition associated with progressive striatal dopamine deficiency secondary to degeneration of dopaminergic neurons in the substantia nigra. Selegiline is currently the most widely used monoamine oxidase-B inhibitor for Parkinson's disease, but has a low and variable bioavailability, and is metabolized to L-methamphetamine and L-amphetamine that carry a risk for potential neurotoxicity. There are two new approaches that circumvent these potential disadvantages. First, selegiline orally disintegrating tablets provide a novel delivery form of selegiline, avoiding first pass metabolism by rapid absorption through the oral mucosa, thus leading to significantly lower plasma concentrations of L-metamphetamine and L-amphetamine. Selegiline orally disintegrating tablets prove to be clinically effective and safe in patients with moderately advanced Parkinson's disease. Second, rasagiline is a new monoamine oxidase inhibitor, without known neurotoxic metabolites. In large clinical trials, rasagiline proves effective as monotherapy in early Parkinson's disease, as well as adjunctive therapy to levodopa in advanced disease. Clinical data suggest, in addition, a disease-modifying effect of rasagiline that may correlate with neuroprotective activity of monoamine oxidase-B inhibitors in animal models of Parkinson's disease.     

Time course of catch-up in adiposity influences adult anthropometry in individuals who were born small for gestational age

Although necessary for a normal final height in individuals who were born small for gestational age (SGA), catch-up growth is associated with drastic changes in body composition that have been suspected to favor the later development of the long-term metabolic complications by promoting central adiposity; however, the specific contribution of catch-up itself on these later complications remains unclear. Therefore, the aim of the study was to characterize the dynamic changes in adiposity during childhood in individuals who were born SGA and to investigate their consequences on adulthood. The magnitude and the time course of postnatal changes in body mass index (BMI) relative to birth and their consequences on adult adiposity were investigated in 127 adults who were born SGA and had available serial anthropometric data in childhood (0-6 y) and adulthood. Catch-up in BMI, observed in 91% of individuals who were born SGA, was mostly completed within the first or second year of age. Overall, adult BMI was correlated with the magnitude of gain in BMI during childhood. However, this effect was significant only when this gain persisted after the first year of life. Similarly, the influence of the magnitude in gain in BMI on the risk for adult BMI >25 kg/m(2) was significantly influenced by the age at which the gain in BMI occurred. In summary, although the extent of catch-up in BMI affects adiposity in adulthood, this effect is mostly deleterious when occurring after 1 y of age, suggesting that a rapid catch-up process should be more suitable than a delayed one. Whether this observation holds through regarding the metabolic syndrome remains to be elucidated.     

Successful match-unrelated donor bone marrow transplantation for congenital erythropoietic porphyria (Günther disease)

Congenital erythropoietic porphyria (CEP; Günther disease; OMIM 263700) is a rare autosomal recessive disorder caused by a deficiency of uroporphyrinogen III synthase (UROS). The deficiency of this enzyme is associated with lifelong overproduction of series I porphyrins which circulate and are deposited in many tissues, causing light-sensitisation and severe damage to skin beginning in childhood. Blistering and scarring of exposed areas may lead to mutilating deformities. We describe two cases: a 4-year-old boy and his first cousin who were cured of CEP by matched unrelated donor bone marrow transplants. Both are alive and disease-free 3 and 2 years post-transplant, respectively. Cutaneous lesions improved dramatically. The correction of the enzyme deficiency was confirmed by measuring erythrocyte UROS activity and urinary porphyrin excretion. Chimerism was complete for both children. Both patients were homoallelic for a novel mutation of the UROS gene, the missense mutation A69T. Conclusion:Considering the severity of the disease, if HLA-matched sibling donor is not available, haematopoietic stem cell transplantation using a matched unrelated donor should be strongly considered for treating congenital erythropoietic porphyria since this is currently the only known curative therapy.     

The use of high-dose daily cabergoline in an adolescent patient with macroprolactinoma

Prolactinomas are rare in children and adolescents but well studied in adults. Dopamine agonists are the treatment of choice for all ages. Bromocriptine is the only agonist approved for use in pediatric patients by the FDA. Cabergoline, a second-generation ergot derivative with a longer half-life, has been used in resistant prolactinomas and as first-line treatment in adults. The authors describe an adolescent boy with a pituitary macroadenoma with an initial prolactin level of 73,777 ng/mL. After failing to respond to bromocriptine and standard-dose cabergoline, he responded well to very high daily doses of cabergoline (1.5 mg daily), with a current prolactin level of 726 ng/mL and notable reduction in tumor size. Escalating doses of cabergoline should be considered in pediatric patients with dopamine-resistant prolactinomas.