Clinical and biochemical aspects of depressive disorders: II. Transmitter/receptor theories

Abstract

The present document is the second of three parts in a review that focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. Various receptor/transmitter theories of depressive disorders are discussed in this section. Specifically, data supporting noradrenergic, serotonergic, cholinergic, dopaminergic, GABAergic, and peptidergic theories, as well as interactions between noradrenergic and serotonergic, or cholinergic and catecholaminergic systems are presented. Problems with the data and future directions for research are also discussed. A previous publication, Part I of this review, dealt with the classification of depressive disorders and research techniques for studying the biochemical mechanisms of these disorders. A future publication, Part III of this review, discusses treatments for depression and some of the controversies in this field.

Fluoxetine Combined with a Serotonin-1A Receptor Antagonist Reversed Reward Deficits Observed during Nicotine and Amphetamine Withdrawal in Rats

“…This hypothesis is consistent with the observation that withdrawal from other drugs of abuse, such as cocaine (Parsons et al 1995) or ethanol (Weiss et al 1996), also is characterized by decreased serotonergic neurotransmission as reflected in decreased in vivo dialysate serotonin levels. Further, considering the strong evidence implicating reduced serotonergic neurotransmission as one of the neurochemical abnormalities associated with depression (for reviews, see Caldecott-Hazard et al 1991;Caldecott-Hazard and Schneider 1992;Heninger et al 1996;Markou et al 1998;Meltzer and Lowy 1988;Willner 1985), it can be hypothesized that there is homology between the symptom of "diminished interest or pleasure" seen in individuals withdrawing from drugs of abuse and the same symptom seen in depressed patients. Decreased dopaminergic neurotransmission is another neurobiological abnormality common to withdrawal from a variety of drugs of abuse, including nicotine (Hildebrand et al 1999;Parsons et al 1995;Weiss et al 1996).…”

“…It is unlikely that these somatic signs in the rat reflect the affective component of drug withdrawal. Nevertheless, the study of both threshold elevations and somatic signs permits the investigation of the effects of manipulations on the various aspects of withdrawal.Based on evidence demonstrating the efficacy of serotonergic antidepressant treatments, reduced cerebrospinal fluid levels of serotonin metabolites, endocrine measures reflecting reduced serotonergic neurotransmission and the exacerbation of depressive symptomatology seen after serotonin (5-HT) depletion in depressed individuals, it is hypothesized that reduced serotonergic neurotransmission underlies at least some aspects or some subtypes of non-drug-induced depressions (for reviews, see Caldecott-Hazard et al 1991; CaldecottHazard and Schneider 1992;Heninger et al 1996;Markou et al 1998;Meltzer and Lowy 1988;Willner 1985). The purpose of the present study was to test the hypothesis that reduced serotonergic neurotransmission mediates some of the affective aspects, not only of non-drug-induced depressions, but also of druginduced depressions.…”

Effects of Repeated Treatment With Fluoxetine and Citalopram, a 5-Ht Uptake Inhibitors on 5-Ht1a and 5-Ht2 Receptors in the Rat Brain.

“…Most tricyclic antidepres-Krak6w, Poland. sants share the property of inhibition of 5-HT and noradrenalin uptake and many of these compounds also antagonize postsynaptic 5-HT receptors. These drugs are able to augment 5-HT transmission by prolonging the residence time of 5-HT in the synaptic cleft (Caldecott-Hazard et al 1991;Wong et al 1990). The majority of antidepressant drugs administered repeatedly to rats, decreased the number of 5-HT2 receptor sites and their function measured as the head-twitch response (Goodwin et al 1984;Green 1987;Peroutka and Snyder 1980).…”

Acetylcholinesterase activity in the pons and medulla oblongata of rats after chronic electroconvulsive shock

“…In laboratory animals, repeated ECS treatment induces changes in noradrenergic neurotransmission which are similar to those produced by chronic antidepressant drugs, including down-regulation of beta-adrenergic receptors and reduced synthesis of cyclic adenosine monophosphate (cAMP) induced by noradrenergic agonists (for a review, see Ref. 2). …”

“…According to this hypothesis, depression may be the result of an overactive cholinergic neurotransmission and reduced noradrenergic activity. Antidepressant drugs (inhibitors of noradrenaline uptake and monoamine oxidase activity) along with ECS seem to improve depression by increasing noradrenergic neurotransmission (2). According to the noradrenergiccholinergic interaction hypothesis, these treatments should lead to a decrease in cholinergic neurotransmission.…”