Presynaptic action of neurotensin on cultured ventral tegmental area dopaminergic neurones
Section snippets
Cell culture
VTA primary cultures were prepared from the brains of neonatal rats (postnatal days 1–3), according to a recently described procedure (Bourque and Trudeau, 2000, Michel and Trudeau, 2000, Trudeau, 2000). Rat pups were cryoanaesthetised and all animal handling conformed to Université de Montréal animal ethics committee guidelines. All efforts were made to minimise the number of animals used and their suffering. In brief, a coronal slice with an approximate thickness of 1.5 mm was cut by hand at
Results
Experiments were performed on primary cultures of rat VTA. These preparations contained both neurones and astrocytes. Dopaminergic neurones could be identified by immunoreactivity against tyrosine hydroxylase (Fig. 1A) and comprised between 30 and 40% of the neuronal population. Other neurones were mostly GABAergic (Michel and Trudeau, 2000), as shown by their immunoreactivity to GABA (not shown) [see also (Sulzer et al., 1998)]. A glial cell monolayer covered most of the coverslip surface.
Discussion
The present results provide evidence that NT modulates cultured dopaminergic neurones through at least two separate mechanisms. First, our spontaneous EPSC and action potential recording experiments indicate that NT acts at a somatodendritic level to enhance cellular excitability (Fig. 1, Fig. 2). A second mechanism at the level of the nerve terminals involves a modulatory function that can regulate the effectiveness of terminal D2-type dopamine receptors that normally inhibit neurotransmitter
Acknowledgements
This work was supported in part by the Canadian Institutes of Health Research (former Medical Research Council of Canada), the EJLB Foundation and the Fonds de la Recherche en Santé du Québec. M.L. was supported by a postdoctoral fellowship from the Natural Sciences and Engineering Research Council of Canada. P.C. and F.J.M. are supported by fellowships from the Groupe de Recherche sur le Système Nerveux Central of the Université de Montréal. P.C. also received support from the Canada
References (58)
- et al.
The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami
J. Biol. Chem.
(1973) - et al.
Presynaptic control of dopamine synthesis and release by excitatory amino acids in rat striatal synaptosomes
Neurochem. Int.
(1994) - et al.
Involvement of potentially distinct neurotensin receptors in neurotensin-induced stimulation of striatal [3H]dopamine release evoked by KCl versus electrical depolarization
Neuropharmacology
(1997) - et al.
Dopamine-dependent contralateral circling induced by neurotensin applied unilaterally to the ventral tegmental area in rats
Brain Res. Bull.
(1985) - et al.
Relationships between structure and duration of neurotensin’s central action: emergence of long acting analogs
Neuropeptides
(1984) - et al.
Dopamine regulation of extracellular glutamate in the nucleus accumbens
Brain Res.
(1997) - et al.
Neurotensin and cholecystokinin microinjected into the ventral tegmental area modulate microdialysate concentrations of dopamine and metabolites in the posterior nucleus accumbens
Brain Res.
(1990) - et al.
Clozapine inhibits synaptic transmission at GABAergic synapses established by ventral tegmental area neurones in culture
Neuropharmacology
(2000) - et al.
A pyridazinyl derivative of gamma-aminobutyric acid (GABA), SR 95531, is a potent antagonist of Cl- channel opening regulated by GABAA receptors
Neuropharmacology
(1987) - et al.
Electrophysiological evidence for putative subtypes of neurotensin receptors in guinea-pig mesencephalic dopaminergic neurons
Neuroscience
(1998)
Neurotensin depolarizes substantia nigra dopamine neurones
Brain Res.
Interactions between neurotensin and dopamine in the brain: an overview
Peptides
Comparative localization of neurotensin receptors on nigrostriatal and mesolimbic dopaminergic terminals
Brain Res.
In vivo presynaptic control of dopamine release in the cat caudate nucleus–III. Further evidence for the implication of corticostriatal glutamatergic neurons
Neuroscience
Facilitation of brain stimulation reward by mesencephalic injections of neurotensin-(1–13)
Eur. J. Pharmacol.
A comparison of the effects of mesencephalic injections of neurotensin(1–13) and neuromedin N on brain electrical self-stimulation
Peptides
Mesencephalic microinjections of neurotensin-(1–13) and its C-terminal fragment, neurotensin-(8–13), potentiate brain stimulation reward
Brain Res.
Evidence for a role of endogenous neurotensin in the initiation of amphetamine sensitization
Neuropharmacology
Cholecystokinin and neurotensin inversely modulate excitatory synaptic transmission in the parabrachial nucleus in vitro
Neuroscience
A subpopulation of dopaminergic neurons in rat ventral mesencephalon contains both neurotensin and cholecystokinin
Brain Res.
Electrophysiological effects of neurotensin on dopaminergic neurones of the ventral tegmental area of the rat in vitro
Neuropharmacology
Neurotensin modulates autoreceptor mediated dopamine effects on midbrain dopamine cell activity
Brain Res.
Comparative effects of neurotensin, neurotensin(8–13) and (D-Tyr(11))neurotensin applied into the ventral tegmental area on extracellular dopamine in the rat prefrontal cortex and nucleus accumbens
Neuroscience
Differential effects of neurotensin on dopamine release in the caudal and rostral nucleus accumbens: a combined in vivo electrochemical and electrophysiological study
Neuroscience
Neurochemical and behavioural effects of neurotensin vs (D-Tyr11)neurotensin on mesolimbic dopaminergic function
Neuropeptides
Neurotensin counteracts apomorphine-induced inhibition of dopamine release as studied by microdialysis in rat neostriatum
Brain Res.
Neurotensin regulates intracellular calcium in ventral tegmental area astrocytes: evidence for the involvement of multiple receptors
Neuroscience
Neurotensin increases the cationic conductance of rat substantia nigra dopaminergic neurons through the inositol 1,4,5-trisphosphate-calcium pathway
Brain Res.
Neurotensin promotes oscillatory bursting behavior and is internalized in basal forebrain cholinergic neurons
J. Neurosci.
Cited by (34)
Detergent-free extraction of a functional low-expressing GPCR from a human cell line
2020, Biochimica et Biophysica Acta - BiomembranesCitation Excerpt :Several in vivo studies have highlighted the possible interaction between neurotensin and dopaminergic system [62]. It has been shown that the neurotensin peptide (NT) can modulate dopamine release in various brain structures [63–68], and that NT and dopamine (DA) colocalize in certain compartments of the brain [69,70]. In addition, NT can regulate the dopaminergic transmission in certain tissues [62,68].
The role of intraamygdaloid neurotensin and dopamine interaction in conditioned place preference
2018, Behavioural Brain ResearchCitation Excerpt :Co-localisation of NT and dopamine (DA) has been shown in the VTA, NAC, prefrontal cortex (PFC) and AMY [19,20]. NT has been revealed to modulate the DA release in various brain structures [20–25]. Our previous findings have shown that NT has positive reinforcing effects after its microinjection into the CeA or into the VP [13,14].
Determination of neurotensin projections to the ventral tegmental area in mice
2018, NeuropeptidesCitation Excerpt :It is therefore critical to define the precise neural mechanisms by which Nts engages the VTA, to understand how it regulates such diverse physiology and how Nts signaling becomes maladaptive in disease. Pharmacologic Nts activates VTA DA neurons (Legault et al., 2002; Seutin et al., 1989; Sotty et al., 2000, 1998; St-Gelais et al., 2004; Werkman et al., 2000), thereby increasing DA release in the NA (Kalivas et al., 1983; Kalivas and Duffy, 1990; Sotty et al., 2000, 1998; Steinberg et al., 1995) that can modify goal directed behaviors. Indeed, intra-VTA Nts has been shown to suppress homeostatic and motivated feeding (Cador et al., 1986; Kelley et al., 1989), increase locomotor activity (Cador et al., 1986; Elliott and Nemeroff, 1986; Feifel and Reza, 1999; Kalivas et al., 1983; Kalivas and Duffy, 1990; Kalivas et al., 1981; Panayi et al., 2005; Steinberg et al., 1994) and support self-administration (Glimcher et al., 1987; Kempadoo et al., 2013; Rompre and Gratton, 1993), conditioned place preference (CPP) (Glimcher et al., 1984; Rouibi et al., 2015) and locomotor sensitization similar to addictive drugs (Elliott and Nemeroff, 1986; Kalivas and Duffy, 1990; Kalivas and Taylor, 1985; Voyer et al., 2017).
Substance P and neurotensin in the limbic system: Their roles in reinforcement and memory consolidation
2018, Neuroscience and Biobehavioral Reviews
- 1
Both authors contributed equally to this work.