Decrease in Brain Serotonin 2 Receptor Binding in Patients With Major Depression Following Desipramine Treatment

Yatham, Lakshmi N.; Liddle, Peter F.; Dennie, Joelle; Shiah, I‐Shin; Adam, Michael J.; Lane, Carol J.; Lam, Raymond W.; Ruth, Thomas J.

doi:10.1001/archpsyc.56.8.705

Cited by 136 publications

(90 citation statements)

References 40 publications

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“…For 5HT synapses, we assessed ligand binding for 5HT 1A and 5HT 2 receptors and the presynaptic 5HT transporter. The two receptors converge on common end points in 5HT cell signaling (Barnes and Sharp, 1999;Morin et al, 1992;Rovescalli et al, 1993) and are key players in 5HT-related mental disorders (Arango et al, 2001;Fujita et al, 2000;Yatham et al, 1999Yatham et al, , 2000; the 5HT transporter regulates the synaptic concentration of 5HT and is the major target for antidepressant drugs (Maes and Meltzer, 1995;Nemeroff, 1998;Nutt, 2002). These three proteins have been evaluated previously for short-term changes evoked by adolescent nicotine treatment (Xu et al, 2001(Xu et al, , 2002.…”

Section: Introductionmentioning

confidence: 99%

Permanent, Sex-Selective Effects of Prenatal or Adolescent Nicotine Exposure, Separately or Sequentially, in Rat Brain Regions: Indices of Cholinergic and Serotonergic Synaptic Function, Cell Signaling, and Neural Cell Number and Size at 6 Months of Age

Slotkin

MacKillop

Rudder

et al. 2006

Neuropsychopharmacol

146

113

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Nicotine is a neuroteratogen that disrupts neurodevelopment and synaptic function, with vulnerability extending into adolescence. We assessed the permanence of effects in rats on indices of neural cell number and size, and on acetylcholine and serotonin (5HT) systems, conducting assessments at 6 months of age, after prenatal nicotine exposure, adolescent exposure, or sequential exposure in both periods. For prenatal nicotine, indices of cell number and size showed few abnormalities by 6 months, but there were persistent deficits in cerebrocortical choline acetyltransferase activity and hemicholinium-3 binding to the presynaptic choline transporter, a pattern consistent with cholinergic hypoactivity; these effects were more prominent in males than females. The expression of 5HT receptors also showed permanent effects in males, with suppression of the 5HT 1A subtype and upregulation of 5HT 2 receptors. In addition, cell signaling through adenylyl cyclase showed heterologous uncoupling of neurotransmitter responses. Nicotine exposure in adolescence produced lasting effects that were similar to those of prenatal nicotine. However, when animals were exposed to prenatal nicotine and received nicotine subsequently in adolescence, the adverse effects then extended to females, whereas the net effect in males was similar to that of prenatal nicotine by itself. Our results indicate that prenatal or adolescent nicotine exposure evoke permanent changes in synaptic function that transcend the recovery of less-sensitive indices of structural damage; further, prenatal exposure sensitizes females to the subsequent adverse effects of adolescent nicotine, thus creating a population that may be especially vulnerable to the lasting behavioral consequences of nicotine intake in adolescence.

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Section: Introductionmentioning

confidence: 99%

Permanent, Sex-Selective Effects of Prenatal or Adolescent Nicotine Exposure, Separately or Sequentially, in Rat Brain Regions: Indices of Cholinergic and Serotonergic Synaptic Function, Cell Signaling, and Neural Cell Number and Size at 6 Months of Age

Slotkin

MacKillop

Rudder

et al. 2006

Neuropsychopharmacol

146

113

View full text Add to dashboard Cite

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“…Finally, most antidepressant drugs either acutely block 5-HT 2A receptors (mirtazapine, mianserin, trazodone, nefazodone, amitriptyline, nortriptyline, imipramine) or decrease the density of 5-HT 2A receptors following chronic drug administration (TCAs; monoamine oxidase inhibitors, MAOIs; atypical antidepressants such as trazodone, mianserin and mirtazapine) (Blackshear and Sanders-Bush, 1982;Conn and Sanders-Bush, 1986;Peroutka and Snyder, 1980;Riblet and Taylor, 1981;Richelson, 2001;Sanders-Bush et al, 1989). Human PET imaging studies have found that chronic treatment with the TCA desipramine decreases 5-HT 2A receptor binding (Yatham et al, 1999). Thus, a wide range of studies at both the preclinical and clinical level lend support to the notion that modulation of 5-HT 2A receptors may be related to depression, suicide and therapeutic responses to antidepressant drugs.…”

Section: Introductionmentioning

confidence: 99%

Regulation of rat cortical 5-hydroxytryptamine2A receptor-mediated electrophysiological responses by repeated daily treatment with electroconvulsive shock or imipramine

Marek

2008

European Neuropsychopharmacology

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Down-regulation of 5-hydroxytryptamine 2A (5-HT 2A ) receptors has been a consistent effect induced by most antidepressant drugs. In contrast, electroconvulsive shock (ECS) up-regulates the number of 5-HT 2A receptor binding sites. However, the effects of antidepressants on 5-HT 2A receptormediated responses on identified cells of the cerebral cortex has not been examined. The purpose of the present study was to compare the effects of the tricyclic antidepressant imipramine and ECS on 5-HT 2A receptor-mediated electrophysiological responses involving glutamatergic and GABAergic neurotransmission in the rat medial prefrontal cortex (mPFC) and piriform cortex, respectively. The electrophysiological effects of activating 5-HT 2A receptors was consistent with 5-HT 2A receptor binding regulation for imipramine and ECS except for the mPFC where chronic ECS decreased the potency of 5-HT at a 5-HT 2A receptor-mediated response. These findings are consistent with the general hypothesis that chronic antidepressant treatments shift the balance of serotonergic neurotransmission towards inhibitory effects in the cortex.

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“…Accordingly, in the present work, we carried out longitudinal evaluations of nicotine administration in adolescence and for up to 1 month after withdrawal of nicotine, comparing the effects in animals with or without prior exposure to prenatal nicotine. We assessed two 5HT receptor subtypes, 5HT 1A and 5HT 2 , that are known to be affected in human depression (Arango et al, 2001;Fujita et al, 2000;Yatham et al, 1999Yatham et al, , 2000. In addition, we evaluated cellular responses mediated through adenylyl cyclase (AC), a signaling pathway that plays critical roles in both dependence and withdrawal (Abreu-Villaça et al, 2003b;Nestler, 1992;Tzavara et al, 2002), and that we previously found to be affected by adolescent nicotine administration and abstinence (AbreuVillaça et al, 2003b;Xu et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Slotkin

Tate

Cousins

et al. 2005

Neuropsychopharmacol

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Offspring of women who smoke during pregnancy are themselves more likely to take up smoking in adolescence, effects that are associated with a high rate of depression and increased sensitivity to withdrawal symptoms. To evaluate the biological basis for this relationship, we assessed effects on serotonin (5-hydroxytryptamine, 5HT) receptors and 5HT-mediated cellular responses in rats exposed to nicotine throughout prenatal development and then given nicotine in adolescence (postnatal days PN30-47.5), using regimens that reproduce plasma nicotine levels found in smokers. Evaluations were then made during the period of adolescent nicotine treatment and for up to one month after the end of treatment. Prenatal nicotine exposure, which elicits damage to 5HT projections in the cerebral cortex and striatum, produced sex-selective changes in the expression of 5HT 1A and 5HT 2 receptors, along with induction of adenylyl cyclase (AC), leading to sensitization of heterologous inputs operating through this signaling pathway. Superimposed on these effects, the AC response to 5HT was shifted toward inhibition. By itself, adolescent nicotine administration, which damages the same pathways, produced similar effects on receptors and the 5HT-mediated response, but a smaller overall induction of AC. Animals exposed to prenatal nicotine showed a reduced response to nicotine administered in adolescence, results in keeping with earlier findings of persistent desensitization. Our results indicate that prenatal nicotine exposure alters parameters of 5HT synaptic communication lasting into adolescence and changes the response to nicotine administration and withdrawal in adolescence, actions which may contribute to a subpopulation especially vulnerable to nicotine dependence.

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Decrease in Brain Serotonin 2 Receptor Binding in Patients With Major Depression Following Desipramine Treatment

Abstract: Depressed patients showed a significant reduction in available 5-HT2 receptors in the brain following desipramine treatment, but it is unknown if this change in 5-HT2 receptors is due to clinical improvement or an effect of desipramine that is unrelated to clinical status.

Cited by 136 publications

References 40 publications

Permanent, Sex-Selective Effects of Prenatal or Adolescent Nicotine Exposure, Separately or Sequentially, in Rat Brain Regions: Indices of Cholinergic and Serotonergic Synaptic Function, Cell Signaling, and Neural Cell Number and Size at 6 Months of Age

Permanent, Sex-Selective Effects of Prenatal or Adolescent Nicotine Exposure, Separately or Sequentially, in Rat Brain Regions: Indices of Cholinergic and Serotonergic Synaptic Function, Cell Signaling, and Neural Cell Number and Size at 6 Months of Age

Regulation of rat cortical 5-hydroxytryptamine2A receptor-mediated electrophysiological responses by repeated daily treatment with electroconvulsive shock or imipramine

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

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