Differential effects of acute and chronic fluoxetine administration on the spontaneous activity of dopaminergic neurones in the ventral tegmental area

Prisco, Simona; Esposito, Ennio

doi:10.1111/j.1476-5381.1995.tb16684.x

Cited by 157 publications

(87 citation statements)

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“…Although a recent study demonstrated that the majority of dorsal raphe neurons that project to the VTA are nonserotoninergic, 46 neuroanatomical studies have revealed 5-HT immunoreactive fibres in the VTA, 47 and there is evidence that the mesolimbic dopaminergic system is under the control of the 5-HT system. 48,49 Alteration of the 5-HT system alters cocaine sensitization As a psychostimulant, cocaine elicits a dose-dependent increase in motor activity in rodents. 50,51 Additionally, cocaineinduced motor effects depend on the number and duration of administrations, where repeated administrations result in increased motor responses (behavioural sensitization).…”

Section: Differential Roles Of Altered Da and 5-ht Systems On Locomotmentioning

confidence: 99%

Selective genetic disruption of dopaminergic, serotonergic and noradrenergic neurotransmission: insights into motor, emotional and addictive behaviour

Isingrini¹,

Perret²,

Rainer³

et al. 2016

jpn

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IntroductionMonoaminergic neurotransmitters, namely dopamine (DA), noradrenaline (NE) and serotonin (5-HT), extensively modulate cognitive, affective, neuroendocrine and motor functions in the brain. 1 The role of the monoaminergic systems in psychi atric pathology has been clearly established based on the observation that effective psychotropic drugs primarily target these systems. [2][3][4] However, the functional subdivision of the monoamine systems indicates a disparity in cerebral distribution, receptor subtypes and mechanisms of action. Unravelling the independent roles of the monoaminergic systems in patients with neuropsychiatric disorders remains a challenge that is complicated by their large anatomic, pharmacological and functional overlaps.At the molecular level, the monoaminergic systems share common properties. The intra-and extracellular concentrations of monoamines are primarily controlled by 2 types of transporters. The plasma membrane transporters (norepinephrine transporter [NET], serotonin transporter [SERT] and dopamine transporter [DAT]) play an essential role in the clearance and recycling of monoamines via uptake from the extracellular space, and the vesicular monoamine transporter (VMAT) accumulates monoamines in synaptic vesicles and is essential for their release. 5 Two VMAT genes have been cloned, 6,7 and although the proteins encoded by these genes are structurally related, they fulfill distinct roles. VMAT1 is primarily expressed in the peripheral nervous system; VMAT2 is primarily expressed in the neurons of the central nervous system. 8,9 The functions of VMAT2 include storage of monoamines, protection of monoamines from cytoplasmic oxi dation and regulation of stimulated monoamine quantal release. 10 Thus, VMAT2 deficiency contributes to a decrease in the synaptic release of monoamines and an increase in the degradation of intracellular monoamines.To better understand the physiologic and behavioural roles of monoaminergic signalling, several investigators have created VMAT2-knockout (KO) mice by disrupting the gene that Background:The monoaminergic transmitters dopamine (DA), noradrenaline (NE) and serotonin (5-HT) modulate cerebral functions via their extensive effects in the brain. Investigating their roles has led to the creation of vesicular monoaminergic transporter-2 (VMAT2) knockout (KO) mice. While this mutation results in postnatal death, VMAT2-heterozygous (HET) mice are viable and show a complex behavioural phenotype. However, the simultaneous alteration of the 3 systems prevents investigations into their individual functions. Methods: To assess the specific role of NE, 5-HT and DA, we genetically disrupted their neurotransmission by creating conditional VMAT2-KO mice with targeted recombination. These specific recombinations were obtained by breeding VMAT2 lox/lox mice with DBHcre, SERTcre and DATcre mice, respectively. We conducted a complete neurochemical and behavioural characterization of VMAT2-HET animals in each system. Results: Conditional VMAT2-KO mice reveale...

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Section: Differential Roles Of Altered Da and 5-ht Systems On Locomotmentioning

confidence: 99%

Selective genetic disruption of dopaminergic, serotonergic and noradrenergic neurotransmission: insights into motor, emotional and addictive behaviour

Isingrini¹,

Perret²,

Rainer³

et al. 2016

jpn

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“…Here too, systemic administration of agonists (most commonly Ro 60-0175) at 5-HT2C receptors decreases DA efflux in the NA (Di Gobert et al, 2000;De Deurwaerdere et al, 2004) and decreases the firing rate of VTA DA neurons (Prisco et al, 1994;Prisco and Esposito, 1995;, 2000Gobert et al, 2000). The inverse agonist SB 206553 (Di Gobert et al, 2000) and the antagonists mesulergine and SB 242084 (Prisco et al, 1994; respectively) increase the firing rate of these neurons.…”

Section: Mesolimbic Pathwaymentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

535

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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“…For example, systemic and microiontophoretic administration of the 5-HT 2C/1B agonist meta-chlorophenylpiperazine (mCPP) decreased the firing rate of VTA DA neurons; the systemic actions of mCPP were antagonized by the 5-HT 2/1A antagonist mesulergine, which alone increased firing rates of a subpopulation of these cells (Prisco et al 1994;Prisco and Esposito 1995). Although 5-HT 2C/2B/1B ligands failed to alter the firing characteristics of DA neurons in the substantia nigra (Kelland et al 1990; but see Stanford and Lacey 1996), the activity of VTA DA neurons is reported to increase following administration of the 5-HT 2C/2B antagonists SB 200646A (Ashby and Minabe 1996) or SB 206553 (Lejeune et al 1997).…”

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confidence: 99%

“…The ability of selective 5-HT 2C antagonists to affect hyperactivity induced by cocaine has not been analyzed, however, non-selective 5-HT 1/2 antagonists have been shown to enhance cocaine-induced hyperactivity (Scheel-Kruger et al 1977;Berman et al 1982;Herges and Taylor 1998; but see Reith 1990 andPeltier et al 1994). Since 5-HT 2C antagonists appear to increase the activity of a subpopulation of VTA DA neurons (Prisco et al 1994;Prisco and Esposito 1995;Ashby and Minabe 1996;Lejeune et al 1997) and 5-HT 2C agonists induce hypomotility (Lucki et al 1989;Kennett 1993;Kennett et al 1996), a 5-HT 2C antagonist would be predicted to increase the locomotor activation observed after cocaine administration. To test this hypothesis, we assessed the ability of the 5-HT 2C/2B antagonist SB 206553 (Forbes et al 1995;Kennett et al 1996) to modulate spontaneous and acute cocaine-induced locomotor activation.…”

mentioning

confidence: 99%

Effects of the 5-HT2C/2B Antagonist SB 206553 on Hyperactivity Induced by Cocaine

McCreary

Cunningham²

1999

Neuropsychopharmacology

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The behavioral effects of cocaine in rodents include the stimulation of locomotor activity and stereotypy as well as convulsions at higher doses (Scheel-Kruger et al. 1977;McCreary and Marsden 1993). Cocaine also serves as a positive reinforcer for operant behavior (de Wit and Wise 1977) and elicits interoceptive stimulus effects easily discriminable from saline . The locomotor stimulant effects have been linked to the inhibition of dopamine (DA) reuptake (Koe 1976) and a subsequent enhancement of DA activation via both DA D 1 and D 2 receptors (Scheel-Kruger et al. 1977;McCreary and Marsden 1993;White et al. 1998). The elevated DA neurotransmission, particularly within the mesoaccumbens pathway originating from DA soma in the ventral tegmental area (VTA) and terminating in the nucleus accumbens (NAc), is especially important in mediating the locomotor, discriminative stimulus and reinforcing effects of cocaine (for review, Amalric and Koob 1993).Despite the pronounced involvement of DA in its in vivo effects, cocaine is not a selective DA reuptake inhibitor as it binds to 5-hydroxytryptamine (5-HT) and norepinephrine (NE) transporters and inhibits the reuptake of 5-HT and NE with at least equal potency and efficacy as that of DA reuptake (Koe 1976). Recent studies of the locomotor stimulant, reinforcing and stimulus effects of cocaine suggest that enhanced 5-HT transmission and subsequent stimulation of 5-HT receptors play a modulatory role in the in vivo effects of cocaine (for reviews, see Cunningham and Callahan 1994;Walsh and Cunningham 1997).The exact contribution of specific 5-HT receptors to the behavioral profile of cocaine has not yet been fully elucidated, largely due to the multiplicity of 5-HT receptors in mammalian systems and the lack of selective Received May 13, 1998; revised August 20, 1998; accepted September 3, 1998. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 20 , NO . 6 5-HT 2C Receptors and Cocaine Hyperactivity 557 ligands for each of the respective receptor subtypes. At least 14 5-HT receptor subtypes have been shown to exist, although the operational characteristics are unknown for some receptors (Hoyer and Martin 1997). The 5-HT 2C receptor subtype (formerly 5-HT 1C ) has received attention as a possible therapeutic target in psychiatric conditions such as psychoses and anxiety (Kennett 1993) and evidence suggests that this receptor is important in the serotonergic regulation of the mesolimbic DA system. The transcript for the 5-HT 2C receptor is richly expressed in DA somatic and terminal field regions, including the VTA and NAc (Hoffman and Mezey 1989;Eberle-Wang et al. 1997).Although not yet established for the VTA, 5-HT 2C mRNA was localized in ␥ -aminobutyric acid (GABA), but not DA, neurons in the substantia nigra suggesting that the influence of 5-HT 2C receptors on DA cell bodies may be indirect (Eberle-Wang et al. 1997). In keeping with the distribution of mRNA, ligand binding studies have demonstrated labeling of 5-HT 2C receptors in the VTA and NAc (Pazos and Palacios 1985;M...

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Differential effects of acute and chronic fluoxetine administration on the spontaneous activity of dopaminergic neurones in the ventral tegmental area

Cited by 157 publications

References 54 publications

Selective genetic disruption of dopaminergic, serotonergic and noradrenergic neurotransmission: insights into motor, emotional and addictive behaviour

Selective genetic disruption of dopaminergic, serotonergic and noradrenergic neurotransmission: insights into motor, emotional and addictive behaviour

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Effects of the 5-HT2C/2B Antagonist SB 206553 on Hyperactivity Induced by Cocaine

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