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P Weinreich

Publications and source records attributed to P Weinreich.

10 recordsLinked to original sources

Dopamine and opiate receptors: localization in the striatum and evidence for their axoplasmic transport in the nigrostriatal and striatonigral pathways.

The axoplasmic transport of dopamine and opiate receptors in the striatonigral and nigrostriatal pathways was investigated by placing coronal knife cuts through these pathways and examining autoradiographically the accumulation of receptors at the site of the cut. In otherwise normal animals build-up of both receptors was found both rostral and caudal to the cut after a survival time of 24 h. Build-up of both receptors was reduced caudal to the cut by prior 6-hydroxydopamine lesions of the substantia nigra-ventral tegmental area, and reduced rostral to the cut by prior kainic acid lesions of the striatum. In addition, it was found by both autoradiographic and membrane binding methods that kainic acid lesions of the striatum produced a larger reduction of striatal opiate compared with dopamine receptors. The results suggest that opiate and dopamine receptors are axonally transported in fibers of both the nigrostriatal and striatonigral pathways possibly to their respective presynaptic terminals. The differential sensitivity of opiate and dopamine receptors in the striatum to local kainic acid lesions suggests the preferential localization of postsynaptic opiate receptors on dendritic trunks and neuronal somata, whereas the major localization of postsynaptic dopamine receptors may be on striatal dendritic spines, which to some extent appear to survive the lesions.

Animals↗

Empirical assessment of identity in anorexia and bulimia nervosa.

Researchers have neglected the study of the self concept of individuals who develop anorexia and bulimia nervosa. Towards rectifying this situation, Identity Structure Analysis (ISA) is introduced as an appropriate framework allowing the specification and empirical testing of postulates regarding disturbed identity development in anorexic disorders. The data presented distinguish a common constellation of identity characteristics in those suffering from anorexia and bulimia nervosa that differentiate them from normal and psychiatric control groups. Their identity pattern tends to be anti-developmental and in a state of 'identity crisis', in which identification conflicts with the maternal metaperspective of self (me as my mother sees me) are especially significant. Further analysis suggest that anorexics are in a phase of 'plummeting' identity crisis, whilst the patients in the sample with bulimia nervosa are in a 'sustained' phase. Future directions for research are noted.

Anorexia Nervosa↗

Multiple binding sites for [3H]clonidine and [3H]WB-4101 in rat brain.

Binding of the alpha-adrenergic agonist [3H]clonidine and the alpha-adrenergic antagonist [3H]WB-4101 exhibited multiple binding site characteristics in both rat frontal cortex and cerebellum. Kinetic analysis of the dissociation of both radioligands in rat frontal cortex suggests two high affinity sites for each ligand. Competition of various noradrenergic agonists and antagonists for [3H]WB-4101 binding yielded shallow competition curves, with Hill coefficients ranging from 0.45 to 0.7. This further suggests multiplicity in [3H]WB-4101 binding. In the rat cerebellum, competition of various noradrenergic drugs for [3H]clonidine binding yielded biphasic competition curves. Furthermore Scatchard analysis of [3H]clonidine binding in rat cerebellum showed two high affinity sites with KD = 0.5 nM and 1.9 nM, respectively. Competition of various noradrenergic drugs for [3H]WB-4101 binding in the rat cerebellum yielded biphasic competition curves. Lesioning of the dorsal bundle with 6-hydroxydopamine did not significantly affect the binding of either [3H]clonidine or [3H]WB-4101. These findings for both [3H]clonidine and [3H]WB-4101 binding in rat frontal cortex and cerebellum can be explained by the existence of postsynaptic binding sites for both 3H ligands.

Adrenergic alpha-Agonists↗

Multiple receptors for brain dopamine.

This study was done to obtain direct in vitro evidence for the possible existence of more than one type of dopaminergic binding site in homogenates of the caudate nucleus from calf brain. Five radioligands for dopaminergic sites were tested. The inhibitions of two agonist radioligands ([3H]dopamine, [3H]apomorphine) by haloperidol, chlorpromazine, or piflutixol were biphasic. The inhibitions of [3H]haloperidol, [3H]spiroperidol, and [3H]dihydroergocryptine binding by dopamine and (-)-norepinephrine were also biphasic. Thus, both 3H-labeled agonists and 3H-labeled antagonists were possibly binding to two high-affinity sites.

Animals↗

Dopamine receptors in the central nervous system.

Dopamine receptors in the central nervous system can be studied by measuring the specific binding of [3H]dopamine, [3H]haloperidol, d-[3H]LSD, [3H]dihydroergocryptine or [3H]apomorphine. The receptors are stereoselectively blocked by +)-butaclamol, a neuroleptic. All neuroleptics inhibit the specific binding of [3H]haloperidol in relation to their clinical potencies. The radioligand that desorbs most slowly from the receptor is [3H]apomorphine, thus making it a reliable ligand for dopamine receptors. Dopamine agonists that compete for [3H]apomorphine binding do so at concentrations that correlate with their potency in stimulating striatal adenylate cyclase. Structure-activity analysis, using [3H]apomorphine, confirms that the active dopamine-mimetic conformation is the beta rotamer of dopamine. Prolonged exposure in vitro of caudate homogenate to high concentrations of dopamine leads to increased binding of [3H]apomorphine or [3H]haloperidol, suggesting receptor "sensitization." Chronic haloperidol treatment of rats leads to an increased number of dopamine/neuroleptic receptors in the striatum, but a decrease in the pituitary.

Adenylyl Cyclases↗

New detection of brain dopamine receptors with (3H)dihydroergocryptine.

Because dihydroergocryptine (DHE) and closely related ergots are dopamine-mimetic agonists, we tested [3H]DHE as a possible ligand for [3H]dopamine receptors in the calf caudate. In order to avoid [3H]DHE from tagging alpha-adrenergic receptors, an excess of 500 nM phentolamine was used to block these sites, permitting the dopamine receptors to be measured separately. Specific binding of [3H]DHE was defined as total binding minus that occurring in the presence of 1 muM (+)-butaclamol. Excess phentolamine reduced the specific binding of [3H]DHE from 328 down to 138 fmol/mg, the difference presumably representing alpha-receptors. The KD for [3H]DHE was 0.55 nM (with or without phentolamine), and this high affinity site was blocked (in the presence of phentolamine) by 250nM apomorphine, 650 nM dopamine, and 1200 mM (minus)-norepinephrine, indicating that[3H]DHE was binding to dopamine receptors. All neuroleptics blocked specific [3H]DHE binding in direct relation to the clinical potency of the neuroleptic. The displacement of specific [3H]DHE binding by dopamine or by norepinephrine (in the presence of phentolamine) revealed two subsets of dopamine receptors.

Animals↗