Endogenous Neurotensin in the Ventral Tegmental Area Contributes to Amphetamine Behavioral Sensitization

Panayi, Fany; Colussi-Mas, Joyce; Lambás‐Señas, Laura; Renaud, Bernard; Scarna, H.; Bérod, Anne

doi:10.1038/sj.npp.1300638

Cited by 42 publications

(53 citation statements)

References 65 publications

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“…This hypothesis was recently proposed from data obtained with another NT receptor antagonist, SR 142948A, demonstrating that a single intra-VTA administration of this compound before an amphetamine injection was sufficient to counteract the induction of behavioral sensitization to this psychostimulant (Panayi et al, 2005), whereas a long-term treatment was required on systemic administration (Panayi et al, 2002).…”

Section: Discussionmentioning

confidence: 89%

“…Pretreatment with an antagonist of the high-affinity NT receptor 1 (NTS1), SR 48692 (Gully et al, 1993), attenuated the locomotor response to an acute cocaine injection and delayed the development of cocaine sensitization (Horger et al, 1994). Furthermore, coadministration of SR 48692 or its analogue SR 142948A (Gully et al, 1997) and amphetamine blunted locomotor sensitization induced by the latter drug (Rompré and Perron, 2000;Panayi et al, 2002Panayi et al, , 2005.…”

Section: Introductionmentioning

confidence: 99%

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Neurotensin Receptor Antagonist Administered during Cocaine Withdrawal Decreases Locomotor Sensitization and Conditioned Place Preference

Felszeghy

Espinosa

Scarna

et al. 2007

Neuropsychopharmacol

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Chronic use of psychostimulants induces enduringly increased responsiveness to a subsequent psychostimulant injection and sensitivity to drug-associated cues, contributing to drug craving and relapse. Neurotensin (NT), a neuropeptide functionally linked to dopaminergic neurons, was suggested to participate in these phenomena. We and others have reported that SR 48692, an NT receptor antagonist, given in pre-or cotreatments with cocaine or amphetamine, alters some behavioral effects of these drugs in rats. However, its efficacy when applied following repeated cocaine administration remains unknown. We, therefore, evaluated the ability of SR 48692, administered after a cocaine regimen, to interfere with the expression of locomotor sensitization and conditioned place preference (CPP) in rats. We demonstrated that the expression of locomotor sensitization, induced by four cocaine injections (15 mg/kg, i.p.) every other day and a cocaine challenge 1 week later, was attenuated by a subsequent 2-week daily administration of SR 48692 (1 mg/kg, i.p.). Furthermore, the expression of cocaine-induced CPP was suppressed by a 10-day SR 48692 treatment started after the conditioning period (four 15 mg/kg cocaine injections every other day). Taken together, our data show that a chronic SR 48692 treatment given after a cocaine regimen partly reverses the expression of locomotor sensitization and CPP in the rat, suggesting that NT participates in the maintenance of these behaviors. Our results support the hypothesis that targeting neuromodulatory systems, such as the NT systems may offer new strategies in the treatment of drug addiction.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Neurotensin Receptor Antagonist Administered during Cocaine Withdrawal Decreases Locomotor Sensitization and Conditioned Place Preference

Felszeghy

Espinosa

Scarna

et al. 2007

Neuropsychopharmacol

Self Cite

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“…Synchronicity in dopamine transients may result from neurotensin release in the VTA. Intra-VTA neurotensin activates dopamine neurons and contributes to behavioral sensitization after administration of psychostimulants (47). The parabrachial nucleus is one source of neurotensinergic projections to the VTA (48) and projects bilaterally to midbrain dopamine neurons (49).…”

Section: Discussionmentioning

confidence: 99%

Cross-hemispheric dopamine projections have functional significance

Fox

Mikhailova

Bass

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson's disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats. In the anesthetized rats, optogenetic and electrical stimulation of dopamine cells elicited physiologically relevant dopamine release in the contralateral striatum. Contralateral release differed between the dorsal and ventral striatum owing to differential regulation by D2-like receptors. In the freely moving animals, simultaneous bilateral measurements revealed that dopamine release synchronizes between hemispheres and intact, contralateral projections can release dopamine in the midbrain of 6-hydroxydopamine-lesioned rats. These experiments are the first, to our knowledge, to show cross-hemispheric synchronicity in dopamine signaling and support a functional role for contralateral projections. In addition, our data reveal that psychostimulants, such as amphetamine, promote the coupling of dopamine transients between hemispheres.dopamine | voltammetry | synchrony | nucleus accumbens | dorsal striatum D opamine neurotransmission modulates arousal and motivation, and is important to the expression of reward-seeking behavior. Dopamine is released on a subsecond timescale during unexpected reward (1, 2), and becomes time-locked to cues that predict reward (3-7). Dopamine transients in the nucleus accumbens (NAc) occur as a result of cell firing in the ventral tegmental area (VTA) (8, 9), and in rats reach concentrations of 50-200 nM before returning to baseline (10, 11). Striatal dopamine transients also occur spontaneously during periods of rest (10, 11), reflecting endogenous dopamine modulation. The magnitude and frequency of dopamine transients increase in response to drugs of abuse (12, 13), which is thought to contribute to their reinforcing properties (14). Although numerous studies have summarized the function of dopamine circuits in reward-based behaviors (15, 16) and motor control (17-19), anatomic descriptions of dopamine projections are conflicting (20-23). Recent evidence suggests that some dopamine neurons project contralateral to their origin (22, 23), contradictory to the uncrossed dopamine system described previously (20, 21). To date, the significance of contralaterally projecting dopamine neurons, and how they may contribute to cross-hemispheric signaling, have not been established.A potential role for contralateral dopamine projections emerged in a recent study on brain stimulation reward (24). When rats were trained to self-stimulate the VTA, infusion of dopamine receptor antagonists in the NAc suppressed stimulation. This effect was seen whether the infusion was contralateral or ipsilateral to the stimulation site, reflecting cross-hemispheric modulation of the behavior. Furthe...

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“…Pre-treatment with an antagonist of the NTS1 receptor, SR48692, reduced the number of rearing induced by acute cocaine injection (Betancur et al, 1998) and delayed the development of cocaine sensitization (Horger et al, 1994 ). Furthermore, the locomotor sensitization to amphetamine could be blocked when the drug was co-administered with SR48692 (Panayi et al, 2005;Panayi et al, 2002;Rompre and Perron, 2000). The aim of this study was to explore the role of endogenous neurotensin on behavioral effects of MDMA, including hyperlocomotion and the acquisition and expression of conditioned place preference.…”

Section: Introductionmentioning

confidence: 99%

Effects of the selective neurotensin antagonist SR 142948A on 3,4-methylenedioxymethamphetamine-induced behaviours in mice

et al. 2008

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Neurotensin is one of the genes previously found up-regulated in mice striatum after acute injection of MDMA (9mg/kg). In order to examine the pharmacological significance of this effect the involvement of the neurotensinergic system in MDMA-induced behaviors was explored in mice using the neurotensin receptor antagonist SR142948A (1mg/kg). We found that acute administration of the antagonist inhibited the MDMA-elicited locomotor activity. SR142948A pretreatment had no effect on the acquisition of conditioned place preference (CPP) to MDMA but abolished the expression of this behavior. We also studied the effects of acute and repeated exposure to MDMA on the mRNA level of neurotensin in mice striatum. Kinetic analysis of the regulation 1, 2, 6 and 12 hours after acute injection of MDMA showed that the drug transiently upregulate neurotensin mRNA in this structure. The time course of the modulation suggests that the effects observed with SR142948A are attributable to the release of a preexisting endogenous pool rather than the newly synthesized peptide. Repeated exposure to MDMA following the same injection pattern used in the CPP paradigm revealed an increase in mRNA level of neurotensin in mice striatum. These results indicate that endogenous neurotensin play a role in both the acute locomotor activity and the expression of CPP induced by MDMA.

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Endogenous Neurotensin in the Ventral Tegmental Area Contributes to Amphetamine Behavioral Sensitization

Cited by 42 publications

References 65 publications

Neurotensin Receptor Antagonist Administered during Cocaine Withdrawal Decreases Locomotor Sensitization and Conditioned Place Preference

Neurotensin Receptor Antagonist Administered during Cocaine Withdrawal Decreases Locomotor Sensitization and Conditioned Place Preference

Cross-hemispheric dopamine projections have functional significance

Effects of the selective neurotensin antagonist SR 142948A on 3,4-methylenedioxymethamphetamine-induced behaviours in mice

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