Adenosine – dopamine receptor interactions in the isolated rat nodose ganglion but not in membranes of dorsal vagal complex

The present study has employed in vitro electrophysiology and radioligand binding assays to determine whether dopamine and adenosine receptors interact with each other on rat vagal afferent neurons. Preincubation of the isolated rat nodose ganglion with the adenosine A_2a agonists CGS 21680 or DPMA (Both 1 μM) resulted in a functional antagonism of the ability of dopamine to depolarise the preparation. Specifically, the concentration-response curve to dopamine was significantly shifted to the right in the presence of CGS 21680 and DPMA. On the other hand, adenosine itself, A₁ and A₃ receptor agonists and ATP were all incapable of modulating the electrophysiological response to dopamine. In contrast to the nodose ganglion, CGS 21680 did not significantly affect the ability of the dopamine D₂ ligands quinpirole or raclopride to displace [¹²⁵I]NCQ298 binding to dopamine D₂ receptors in membranes prepared from rat dorsal brain stem. These data indicate the presence of an interaction between high affinity adenosine A₂ receptors and dopamine D₂ receptors on the soma of rat vagal afferent neurons, whereas the situation in the brain stem remains less clear. Received: 17 September 1996 / Accepted: 20 October 1996     

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

Auditory event-related potentials and cognitive function of preterm children at five years of age.

OBJECTIVE: In our previous study, auditory event-related potentials (AERPs) in preterm 1-year-old children had a positive deflection at 150-350 ms that correlated positively with their 2-year neurodevelopmental outcome. In a study of the same subjects at age 5, our aim was to assess AERPs and their relationship to neuropsychological test results. METHODS: Preterm small (SGA, n=13), appropriate for gestational age (AGA, n=15), and control (n=13) children were assessed with an Easy paradigm presenting a large frequency change accompanied with occasional novel sounds, and a Challenging paradigm presenting small frequency and duration changes with a rapid rate. The preterm children underwent neurocognitive tests. RESULTS: Easy paradigm. The P1 response to frequency deviant was smaller and MMN larger in the preterm than in the control children. Challenging paradigm. The P1 response to standard, frequency, and duration deviants was smaller in the preterm than in the control children. The N2 response to frequency deviant was larger in the preterm than in the control children. AGA and SGA children had similar AERPs. The P1, N2, and MMN amplitudes correlated with verbal IQ and NEPSY language subtests. CONCLUSIONS: Small P1 response(s) appears to be typical for preterm children. SIGNIFICANCE: Small P1 response in preterm children may suggest altered primary auditory processing.     

The incidence of error in young children's Wh-questions.

Many current generativist theorists suggest that young children possess the grammatical principles of inversion required for question formation but make errors because they find it difficult to learn language-specific rules about how inversion applies. The present study analyzed longitudinal spontaneous sampled data from twelve 2-3-year-old English speaking children and the intensive diary data of 1 child (age 2;7 [years;months] to 2;11) in order to test some of these theories. The results indicated significantly different rates of error use across different auxiliaries. In particular, error rates differed across 2 forms of the same auxiliary subtype (e.g., auxiliary is vs. are), and auxiliary DO and modal auxiliaries attracted significantly higher rates of errors of inversion than other auxiliaries. The authors concluded that current generativist theories might have problems explaining the patterning of errors seen in children's questions, which might be more consistent with a constructivist account of development. However, constructivists need to devise more precise predictions in order to fully explain the acquisition of questions.     

CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case-control study of female patients and several ethnic groups in the Israeli Jewish population.

The human small-conductance Ca(2+)-activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family-based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co-morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case-control analysis that has demonstrated a significant over-representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co-morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive-compulsive disorder (OCD) co-morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.