Serotonin–dopamine interaction: an overview

Abstract

Central serotonergic and dopaminergic systems play a critical role in the regulation of normal and abnormal behaviours. Moreover, recent evidence suggests that the dysfunction of dopamine (DA) and serotonin (5-hydroxytriptamine, 5-HT) neurotransmission might underlie the pathophysiology of neuropsychiatric disorders, including depression, schizophrenia, attention deficit hyperactivity disorders, drug abuse, Gilles de la Tourette's syndrome and Parkinson's disease.Keywords: serotonin; dopamine; serotonin receptors; substantia nigra; ventral tegmental area; neuropsychiatric disordersThe interaction between the two amines in the brain, in normal and pathological conditions, is an intriguing research field and a better understanding will provide new pharmacological approaches for the treatment of several neuropsychiatric disorders. An extensive scientific literature has investigated the role of serotonin (5-hydroxytriptamine, 5-HT) in the control of central dopamine (DA) systems, and their dysfunction in pathological conditions. In neuropsychiatric disorders, the involvement of 5-HT and DA has been indicated and singled out and new therapeutic approaches suggested. Nevertheless, the interaction between 5-HT and DA systems is far from being completely revealed.The interaction between 5-HT and DA in the brain is a research topic that has raised the interest of many scientists working in the field of neuroscience since the first demonstration of the presence of monoamine-containing neurons in the mid-1960s. Thus, a seminal work by Fuxe (1965) reported the presence of 5-HT-containing terminals in both the substantia nigra (SN) and the ventral tegmental area (VTA). It was subsequently found that serotonergic nerve terminals originating from the dorsal raphe nucleus (DRN) innervated both the SN and the VTA (Steinbusch, 1981), whereas 5-HT fibres arising from median raphe nucleus (MNR) innervated the VTA but not the SN (Fibiger and Miller, 1977;Azmitia and Segal, 1978). Based on those anatomical studies, several investigators began to study the behavioural, biochemical and electrophysiological relevance of the neuroanatomical findings. Further impetus was given to this research by the increasing evidence that most psychotropic drugs, including antidepressants, antipsychotics, opioids, anxiolytics and psychostimulants, exerted their pharmacological actions by interfering with serotonergic and dopaminergic transmission. An

Functional anatomy of 5-HT2A receptors in the amygdala and hippocampal complex: relevance to memory functions

“…Taken together the results discussed here regulation of the various amygdala/hippocampal functions (Pralong et al 2002;Harvey 2003;Hensler 2006). Moreover, many neurological and psychiatric diseases, especially affective disorders, are characterized by a serotonergic dysfunction in these regions (Pralong et al 2002;Hensler 2006;Shin et al 2006;Esposito et al 2008, Di Giovanni et al 2011. Among the plethora of 5-HT receptors (Rs), 5-HT 2A Rs have received considerable attention because of their distribution in these areas, relative high affinity for atypical antipsychotics, and their involvement in the etiology of psychiatric diseases (Gray and Roth 2001;Meltzer and Huang 2008) and memory impairments (de Quervain et al 2003).…”

Oral administration of 5‐hydroxytryptophan (5‐HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task

“…Several studies have demonstrated that 5-HT originating in the raphe nuclei has an inhibitory effect on dopaminergic function in both the mid-and forebrain (Kapur and Remington, 1996;Schmidt and Fadayel, 1995), although it should be noted that such interactions between DA and 5-HT in the brain are complex and receptor-subtype dependent (Di Esposito et al, 2008). Decision making on the IGT under ambiguity (but not under risk) has also been shown to be significantly affected by particular 5-HT transporter polymorphisms, which further implicates the actions of 5-HT as central to this type of decision making (Stoltenberg and Vandever, 2010).…”

Acute dopamine and/or serotonin depletion does not modulate mismatch negativity (MMN) in healthy human participants

“…We have previously shown that simultaneous depletion of 5-HT and DA using combined monoamine depletion (CMD) impairs sustained attention ) and sensory gating (Mann et al 2008). Given the complex interaction between these systems (Roccatagliata et al 1979;Guiard et al 2008;Esposito et al 2008;Di Matteo et al 2008), it is possible that MMN may be more sensitive to global changes in both 5-HT and DA function.…”