ABSTRACT
UNLABELLED: Clonidine is a partial agonist at brain alpha(2)-adrenoceptors (alpha(2)AR), but also has high affinity (K(D) = 51 nM) in homogenate binding assays for non-adrenergic imidazoline-binding sites (I-sites; imidazoline receptors). Herein, an autoradiographic comparison of [3H]-clonidine binding to I-sites and alpha(2)AR in sections of human brain is reported. For I-sites, the adrenergic component of 50 nM [3H]-clonidine binding was masked with either 60 microM norepinephrine (NE; alpha(2)AR agonist) or 12.5 microM methoxy-idazoxan (MIDX; selective alpha(2)AR antagonist), whereas the remaining non-adrenergic sites were studied by displacement with 20 microM cirazoline. Levels of [3H]-clonidine binding to alpha(2)AR and I-sites, determined in adjacent tissue sections, were positively correlated across 27 brain regions (p = 0.0003; r(2) = 0.385). The principal olivary nucleus and the rostral portion of the ventrolateral medulla had highest ratios of I-sites: alpha(2)AR (>4:1). Quantitative transepts drawn across hippocampal images revealed alpha(2)AR enrichments in the CA-1 and inner molecular layers of the dentate gyrus-areas not enriched in I-sites. Competition curves were generated for I-sites in caudate sections using 10 ligands known to distinguish between I(1) and I(2) subtypes. The rank-order of affinities were cirazoline > harmane > BDF6143 > idazoxan = tizanidine (affinities of agmatine, efaroxan, moxonidine, NE, and oxymetazoline were too low to be reliable). Only the endogenous I-site ligand, harmane, had a monophasic displacement curve at the non-adrenergic sites (Ki = 521 +/- 12 nM). IN CONCLUSION: 1) the distribution of non-adrenergic [3H]-clonidine binding sites in human brain sections was correlated with, but distinct from alpha(2)AR; and 2) the affinities of these sites was distinct from alpha(1)AR, alpha(2)AR, I(1) or I(2) sites as previously defined in membrane binding assays. The properties of this non-adrenergic [3H]-clonidine binding site are consistent with I-sites previously labeled by [3H]-cirazoline in rat brain.
Subject(s)
Brain/drug effects , Clonidine/pharmacokinetics , Neurons/drug effects , Receptors, Adrenergic, alpha-2/drug effects , Receptors, Drug/drug effects , Adult , Aged , Aged, 80 and over , Binding Sites/drug effects , Binding Sites/physiology , Brain/cytology , Brain/metabolism , Female , Humans , Imidazoline Receptors , Male , Middle Aged , Neurons/cytology , Neurons/metabolism , Radioligand Assay , Receptors, Adrenergic, alpha-2/metabolism , Receptors, Drug/metabolism , TritiumABSTRACT
Culture plays a significant role in shaping behaviour. When assessing patients from a different culture, mental health experts have to ascertain which behaviors are culturally determined and which are evidence of pathology. Suggestions are made as to how the forensic assessment process can take cultural factors into account.
Subject(s)
Cross-Cultural Comparison , Forensic Psychiatry , Mental Disorders/diagnosis , Humans , Social ValuesABSTRACT
A case is presented of a socially isolated married couple who developed a shared paranoid disorder preceded by their cannabis abuse with the wife initiating the delusions. After the couple were separated the wife feared that she would be killed and assaulted her child and mother. Delusions in the pair ceased quickly and a return to cohabitation did not result in relapse in the absence of cannabis abuse.