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W Regenold

Publications and source records attributed to W Regenold.

6 recordsLinked to original sources
PubMed1994

Paralimbic hypoperfusion in unipolar depression.

METHODS: Relative regional cerebral blood flow was measured with SPECT using 99mTc-hexamethylpropyleneamine oxime in 13 patients with severe unipolar depression that was nonresponsive to drug therapy and 11 age-matched nondepressed controls. RESULTS: All patients were clinically depressed and taking antidepressant drugs at the time of the study. The relative blood flow was significantly decreased bilaterally in the frontal cortex, anterior temporal cortex, anterior cingulate gyrus and caudate in the depressed patients compared with the nondepressed healthy controls. The greatest decreases were seen in the paralimbic regions, specifically, the inferior frontal and cingulate cortex. No significant changes were seen in the parietal cortex, occipital cortex or thalami. Psychiatric rating scales correlated poorly with regional blood flow, except for the degree of psychomotor slowing, which was negatively correlated with frontal and cingulate perfusion. CONCLUSION: These findings implicate selective dysfunction of paralimbic brain regions in clinically depressed patients, independent of their medication use, and support the concept of specific neural systems that regulate mood. Recognition of these regional abnormalities may have clinical utility in both the diagnosis and treatment of depression.

Adult↗
PubMed1990

Post-training injection of the acetylcholine M2 receptor antagonist AF-DX 116 improves memory.

The present study examined the effect of systemic post-training administration of the acetylcholine muscarinic M2 receptor antagonist AF-DX 116 on the acquisition of two 8-arm radial maze tasks. On a win-stay visual discrimination task, a light cue signalled the location of food in 4 randomly selected maze arms, and rats were required to visit each of the 4 lit arms twice within a trial. Rats were given one trial per day and injected immediately post-training on day 5. AF-DX 116 (0.5 and 1.0 mg/kg) significantly improved win-stay acquisition relative to vehicle-injected controls. On a win-shift task, rats were allowed to visit 4 randomly selected maze arms, followed by a delay period. After the delay, rats were returned to the maze for a retention test in which only those 4 arms not visited prior to the delay contained food. On the test (i.e. drug) trial, rats were removed from the maze after the first 4 choices and injected with AF-DX 116 or vehicle. The retention test was given following an 18 h delay. AF-DX 116 (2.0 mg/kg) significantly improved retention relative to vehicle controls. When the injections were given 2 h post-training, no effect on retention was observed in either task. The results demonstrate that post-training injection of the selective M2 receptor antagonist AF-DX 116 improves memory in a time-dependent manner. The findings may have implications for the cholinergic pharmacotherapy of Alzheimer's disease.

Animals↗
PubMed1989

Characterization of [3H]AF-DX 116 binding sites in the rat brain: evidence for heterogeneity of muscarinic-M2 receptor sites.

This study shows that [3H]AF-DX 116 binds specifically, saturably, and with high affinity to putative muscarinic-M2 receptor sites in the rat brain. In homogenates of the hippocampus, cerebral cortex, striatum, thalamus, and cerebellum, [3H]AF-DX 116 appears to bind two subpopulations of muscarinic sites: one class of higher affinity sites (Kd less than 4.0 nM) and one class of lower affinity sites (Kd greater than 50 nM, except in the cerebellum). The apparent maximal capacities (Bmax) of [3H]AF-DX 116 sites in forebrain tissues ranged between 34 and 69 fmol/mg protein for the higher affinity site, and between 197 and 451 fmol/mg protein for the lower affinity site. In cerebellar homogenates, the maximal capacity of [3H]AF-DX 116 binding sites was 10.4 +/- 0.4 (Kd = 1.9 +/- 0.2 nM) and 39.1 +/- 2.6 (Kd = 26 +/- 7 nM) fmol/mg protein for the higher and the lower affinity site, respectively. Determination of the Kd for the higher and lower affinity [3H]AF-DX 116 sites from association and dissociation constants yielded similar values to those obtained from the saturation data. The ligand selectivity pattern reveals that AF-DX 116 is more potent than (-)QNB greater than atropine greater than methoctramine greater than 4-DAMP greater than gallamine greater than NMS greater than carbamylcholine greater than oxotremorine greater than pirenzepine much greater than nicotine in competing for the higher affinity [3H]AF-DX 116 sites. With few exceptions, the pattern was similar for the lower affinity sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Quantitative autoradiographic distribution of [3H]AF-DX 116 muscarinic-M2 receptor binding sites in rat brain.

The distribution of muscarinic-M2 receptors in rat brain was investigated by in vitro autoradiography using [3H]AF-DX 116, a putative probe for the muscarinic-M2 receptor subtype. Incubation of rat brain coronal sections with 10 nM [3H]AF-DX 116 showed highest binding site densities in discrete areas such as the superior colliculus and certain thalamic and brainstem nuclei, similar to the distribution reported for [2H]acetylcholine/M2 sites. [3H]AF-DX 116 site densities were markedly lower in forebrain areas such as cortex, striatum, and hippocampus, in contrast to the distribution seen for [3H]pirenzepine-M1 binding sites, which were concentrated in these forebrain areas; however, differential patterns of labeling were observed for the two muscarinic-M2 probes, [3H]AF-DX 116 and [3H]acetylcholine, in the hippocampal formation. Although [3H]AF-DX 116 binding was broadly distributed in multiple subfields of the hippocampus, [3H]acetylcholine binding was discretely distributed in a manner resembling that of acetylcholinesterase staining. This suggests the existence of muscarinic-M2 subtypes in the CNS, especially in the hippocampal formation.

Animals↗
PubMed1989

Characterization and quantitative autoradiographic distribution of [3H]acetylcholine muscarinic receptors in mammalian brain. Apparent labelling of an M2-like receptor sub-type.

[3H]Acetylcholine receptor binding characteristics (under muscarinic conditions) have been investigated using membrane binding assays and in vitro receptor autoradiography. In rat, guinea-pig and monkey brain membrane preparations, [3H]acetylcholine binds with high affinity (25-50 nM) to an apparently single class of sites which is differentially distributed across brain regions. The ligand selectivity pattern reveals that the potency of (-)quinuclidinyl benzylate is greater than (greater than) atropine greater than scopolamine greater than oxotremorine greater than carbamylcholine greater than pirenzepine greater than methylcarbamyl-choline = nicotine in competing for [3H]acetylcholine binding sites, indicating that [3H]acetylcholine selectively binds to muscarinic sites under these incubation conditions. Moreover, the low potency of pirenzepine suggests that [3H]acetylcholine does not label a significant proportion of the M1 receptor sub-type but most likely binds to putative M2-like receptor sites. This hypothesis is also supported by the autoradiographic distribution of [3H]acetylcholine binding sites in all species studied here. High densities of [3H]acetylcholine binding sites are seen in various nuclei of the medulla and pons, certain thalamic nuclei, medial septum, laminae III, V and VI of the cortex and just above the pyramidal cell layer of the hippocampus. Such localization is much different from that seen with the non-selective antagonist [3H]quinuclidinyl benzylate and the selective M1 receptor ligand [3H]pirenzepine, although it resembles that of the selective M2 receptor antagonist [3H]AF-DX 116. Thus, [3H]acetylcholine apparently mostly binds with high affinity mainly to non-M1 muscarinic receptor types in mammalian brain tissues. Moreover, the ligand selectivity pattern and in vitro receptor autoradiographic data suggest that at low concentrations (10-20 nM) most of [3H]actylcholine labelled sites are of the M2-like receptor class.

Acetylcholine↗