Current Medical Diagnosis & Treatment in Psychiatry


The emergence of molecular neurobiology has profoundly changed the traditional focus of neuropsychopharmacologic research, shifting it toward events occurring beyond the receptors. One can now entertain the possibility that abnormal behavior patterns—affective, cognitive, and somatosensory—might be the consequence of a disarray in the temporal regulation of gene expression in response to internal (ie, neurohumoral, endocrine) and external (ie, environmental) stimuli that have rendered the individual vulnerable to psychiatric disorder. The demonstration that a nurturing defect in mice is linked to the absence of transcription factor Fos B in the preoptic area of the hypothalamus suggests that this transcription factor controls a complex behavior.

Several primary variables are involved in the effect of neuropharmacologic agents and psychotherapy: the neurotransmitters 5-HT, dopamine, norepinephrine, acetylcholine, GABA, and glutamate, acting via various subtypes of receptors; perhaps nitrous oxide and carbon monoxide; and others that are virtually unknown. Second messengers are fewer, but the number of transcription factors is enormous. It has been estimated that the human genome encodes as many as 3000 different gene-specific transcription factors. The nuclear import of these proteins is modulated in response to external stimuli whose transduction is modified by psychotropic (and other neuropharmacologic) agents. It is predicted that the nascence of molecular neuropsychopharmacology will enable the development of new, more effective psychotropic drugs and will provide the foundation for a molecular biological psychiatry.

Basic Neuropharmacology

Cooper JR, Bloom FE, Roth RH: The Biochemical Basis of Neuropharmacology. Oxford University Press, 1996.
Goodman LS, Gilman A: The Pharmacological Basis of Therapies. McGraw-Hill, 1996.
Psychotropic Drugs

Barden N, Reul JMHM, Holsboer F: Do antidepressants stabilize mood through actions on the hypothalamic-pituitary-adrenocortical system? Trends Neurosci 1995; 18:6.  [PMID: 7535490]

Bourin M, Baker GB: Do G proteins have a role in antidepressant actions? Eur Neuropsychopharmacol 1996;6:49.  [PMID: 8866938]

Budziszewska B, Siwanowicz J, Przegalinski E: The effect of chronic treatment with antidepressant drugs on the corticosteroid receptor levels in the rat hippocampus. Pol J Pharmacol 1994;46:147.  [PMID: 8000446]

Fitzgerald LW et al: Regulation of cortical and subcortical glutamate receptor subunit expression by antipsychotic drugs. J Neurosci 1995;15:2453.  [PMID: 7891180]

Goodman LS, Gilman A: The Pharmacological Basis of Therapies. McGraw-Hill, 1996.

Manji HK, Potter WZ, Lenox RH: Signal transduction pathways: molecular targets for lithium’s actions. Arch Gen Psychiatry 1995;52:531.  [PMID: 7598629]

Nibuya M, Nestler EJ, Duman RS: Chronic antidepressant administration increases the expression of CREB in rat hippocampus. J Neurosci 1996;16:2365.  [PMID: 8601816]

Rossby SP, Sulser F: Antidepressants: beyond the synapse. Pages 195–212 in: Skolnick P (editor): Antidepressants: New Pharmacological Strategies. Humana Press, 1997.

Rossby SP et al: Norepinephrine-independent regulation of GRII mRNA in vivo by a tricyclic antidepressant. Brain Res 1995;687:79.  [PMID: 7583316]

Vetulani J et al: A possible common mechanism of action of antidepressant treatments: reduction in the sensitivity of the noradrenergic cyclic AMP generating system in the rat limbic forebrain. Naunyn-Schmiedeberg’s Arch Pharmacol 1976;293:109.

Mechanisms of Regulation of Receptor Function

Brown JR et al: Defect in nurturing in mice lacking the immediate early gene fosB. Cell 1996;86:297.  [PMID: 8706134]

Ferguson SG et al: Role of phosphorylation in agonist-promoted 2-adrenergic receptor sequestration. J Biol Chem 1995;270:24782. [PMID: 7559596]

Premont RT, Inglese J, Lefkowitz RJ: Protein kinases that phosphorylate activated G protein–coupled receptors. FASEB J 1995;9:175.  [PMID: 7781920]

Westphal RS, Backstrom JR, Sanders-Bush E: Increased basal phosphorylation of the constitutively active serotonin 2C receptor accompanies agonist-mediated desensitization. Mol Pharmacol 1995;48:200.  [PMID: 7651352]

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