Eric R. Larson

Cellular distribution of the rat D4 dopamine receptor protein in the CNS using anti-receptor antisera

A polyclonal antiserum was generated against a unique peptide fragment in the rat D4 dopamine (DA) receptor. The titer was monitored using solid-phase ELISA and once it was established, specificity was assessed using Chinese Hamster Ovary (CHO) cells, stably transfected with the full-length cDNA for the rat D4 DA receptor. Immunofluorescent staining produced by incubation with the anti-D4 DA receptor antiserum was selective for D4 DA receptor-transfected CHO cells, and was expressed at their cell membranes and cytoplasm. Attenuated staining for D4 DA receptor protein was visible in untransfected, K1 CHO cells, and in D2 or D3 DA receptor-transfected CHO cells. The regional and cellular CNS distribution patterns for the D4 DA receptor subtype were examined, and illustrated significant protein levels within the frontal (FCx) and parietal cortices. Lesser amounts of receptor protein staining occurred in the thalamus, globus pallidus, hippocampus, cerebellar vermis, and very low expression was detected in the striatum (CPu). D4 DA receptor protein staining was correlated with the cellular expression of its mRNA transcripts in these same brain regions using concurrent fluorescent analyses. The homologous coincidence in staining patterns for the D4 DA receptor transcripts and encoded proteins in identified neurons of the FCx and CPu showed variations in receptor expression in these identified basal ganglia pathways.

Working memory and inhibitory control among manic and euthymic patients with bipolar disorder

Bipolar disorder (BPD) is a severe psychiatric illness that is characterized by episodes of extreme mood states. The affective components of bipolar disorder have been studied extensively, but only recently have investigators begun to systematically examine its cognitive concomitants. Although executive dysfunction has been reported in this population, especially while patients are manic, the tasks administered in many previous studies have made it difficult to determine the specific executive abilities that were compromised. The present study examined 15 patients with bipolar disorder who were manic, 18 who were euthymic, and 18 healthy participants. Tests were selected to evaluate two specific aspects of executive functioning in these participants. The Object Alternation Task was given as a measure of inhibitory control, and the Delayed Response Task was included as a measure of spatial delayed working memory. All groups performed similarly on the Delayed Response Task. On the Object Alternation Task, however, the manic and euthymic patients committed significantly more perseverative errors than healthy participants. These results indicated that patients in the present sample had relatively normal working memory abilities, but had a deficit in behavioral self-regulation, which was evident across mood states.

Cellular distribution of the rat D1B receptor in central nervous system using anti-receptor antisera

Polyclonal antisera have been generated against two unique polypeptide fragments in the rat D1B dopamine (DA) receptor, as deduced from the cDNA sequence. Antisera titers were monitored using solid-phase ELISA. Once the titers were established, antisera specificity was determined using Chinese Hamster ovary (CHO) cells, stably transfected with the full-length cDNA for the rat D1B DA receptor. Immunoreactivity following staining with either anti-D1B DA receptor antisera was equivalent, selective for the D1B DA receptor-transfected CHO cells, and expressed at their membrane and within the cell cytoplasm. Minimal immunofluorescent staining for D1B DA receptor proteins was detected in untransfected CHO cells, or in D1A DA receptor-transfected CHO cells. The regional and cellular distribution patterns for the D1B DA receptor subtype were examined in various brain areas and illustrated significant protein levels within the frontal and parietal cortices and in the hippocampus and dentate gyrus. Lesser amounts of receptor protein staining were seen in the dorsal striatum, olfactory tubercle, and cerebellar vermis. D1B DA receptor protein staining was correlated with the cellular expression of D1B DA receptor mRNA transcripts in these same brain regions using concurrent fluorescent analyses. The homologous coincidence in staining patterns for the D1B DA receptor transcripts and encoded proteins in identified neurons of the frontal cortex and striatum showed variations in receptor expression in these identified basal ganglia pathways.

COEXPRESSION OF STRIATAL DOPAMINE RECEPTOR SUBTYPES AND EXCITATORY AMINO ACID SUBUNITS

The striatal cellular coexpression patterns for the D1A and D2 dopamine (DA) receptor subtypes and the ionotropic excitatory amino acid (EAA) subunits of the N‐methyl‐D‐aspartate (NMDA‐R1) and the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) (GluR1 and GluR2/3) receptor subunits were examined morphologically. Their coincidence was assessed by visualization of mRNA transcripts, localization of encoded receptor proteins, and binding analysis using concurrently paired methods of fluorescence detection. The findings indicated that 1) mRNA transcripts for both receptor systems were detected in the medium‐sized neuron population, and the distribution of receptor message closely reflected protein and binding patterns, with the exception of the GluR1 subunit; 2) both DA receptor mRNA transcripts were coexpressed with each ionotropic EAA receptor subunit examined and with each other, and NMDA and AMPA receptor subunits also showed coincident expression; 3) D1A DA receptor protein was detected in neurons which coexpressed EAA subunit proteins; and 4) GluR2/3 and NMDA‐R1 subunit proteins were coexpressed in medium‐sized neurons which also demonstrated D2 DA receptor binding sites. These findings suggest morphological receptor “promiscuity” since the coexpression patterns between DA and EAA receptors were found in all permutations. The results provide a spatial framework for physiological findings describing functional interactions between the two DA receptor types and between specific DA and EAA receptors in the striatum. Synapse 26:400–414, 1997.

The Effects of Brief Interventions on Children's Playmate Preferences for a Child Sitting in a Wheelchair

More knowledge is needed about interventions that facilitate the acceptance of children with chronic conditions, like physical disabilities. In this study, we examined the impact of scripts, presenting either positive or explanatory information, on young childrens attitudes about a line drawing of either a typical child or one in a wheelchair. Our findings indicated that gender and age were significantly related to childrens perceptions. Girls provided higher playmate preference ratings for both the typical child and the one sitting in a wheelchair than boys, and older children (ages 6 years, 4 months to 9 years) reported higher ratings than younger children. Physical status of the child in the line drawing did not impact childrens opinions. It may be that young children do not hold negative attitudes toward peers who are wheelchair-bound. Because no stigma was attached to the child in either condition, type of information did not influence childrens attitudes. Further research will provide information about what types of interventions improve the acceptance of young children with chronic conditions.

Dopamine receptor binding on identified striatonigral neurons

Dopamine receptors have been divided into two families, known as D1 and D2, based on their ability to bind distinct ligands, and their use of separate post-synaptic transduction systems. Determining the specific cellular location for these dopamine receptors in the striatum is important to the design of drug treatments for disorders with suspected dopaminergic involvement such as Parkinsons disease. This study examined the binding of D1 and D2 antagonist ligands on identified striatonigral neurons using in vitro fluorescent techniques. The results indicate that striatonigral neurons express both pharmacological subfamilies of dopamine receptor binding sites.

Neuropsychological Findings in a Case of Punding Before and After Cessation of Pramipexole

Clinical neuropsychologists are well trained to recognize neurological and psychiatric conditions that impact behavior, but tend to have less familiarity with iatrogenic consequences of various pharmacological treatments. One such consequence is the development of an impulse control disorder (ICD), which can result from treatment with dopamine agonists. Knowledge of ICDs is important because they can mimic obsessive-compulsive disorder, mania, or the behavioral variant of frontotemporal dementia. The current case examines a patient who developed punding, which is a type of ICD characterized by repetitive behavior, as a result of treatment with pramipexole. Neuropsychological testing was conducted before and after cessation of pramipexole, and showed that the removal of the medication was consistent with improvement in frontal-subcortical-mediated cognitive functions. Findings suggest that neuropsychologists should be familiar with the symptoms of ICDs and incorporate such knowledge into their case conceptualizations.