High‐affinity neurotensin receptors in the rat nucleus accumbens: Subcellular targeting and relation to endogenous ligand

Pickel, Virginia M.; Chan, June; Donne, Karen T. Delle; Boudin, Hélène; Pélaprat, Didier; Rostène, William

doi:10.1002/cne.1198

Cited by 37 publications

(11 citation statements)

References 80 publications

(84 reference statements)

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“…Moreover, NTS1 is highly expressed postsynaptically in the ventral striatum which consists of the NAc (Pickel et al, 2001). Thus, we examined if PD149163 microinjection into the NAc reduces locomotion.…”

Section: Resultsmentioning

confidence: 99%

Activation of neurotensin receptor type 1 attenuates locomotor activity

et al. 2014

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Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders.

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Section: Resultsmentioning

confidence: 99%

Activation of neurotensin receptor type 1 attenuates locomotor activity

et al. 2014

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“…NT1 is found in LS, BNST, PVN, cortex, nucleus accumbens, amygdala, substantia nigra, and ventral tegmental area (VTA) (Boudin et al, 1996, Alexander and Leeman, 1998, Binder et al, 2001a, Pickel et al, 2001, Rowe et al, 2006). NT2 is expressed in BNST, nucleus accumbens, preoptic area (including MPOM), amygdala, SN, VTA, PAG, and dorsal raphe (Mazella et al, 1996, Sarret et al, 1998, Walker et al, 1998, Sarret et al, 2003, Caceda et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Neurotensin inversely modulates maternal aggression

et al. 2009

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Neurotensin (NT) is a versatile neuropeptide involved in analgesia, hypothermia, and schizophrenia. Although NT is released from and acts upon brain regions involved in social behaviors, it has not been linked to a social behavior. We previously selected mice for high maternal aggression (maternal defense), an important social behavior that protects offspring, and found significantly lower NT expression in the CNS of highly protective females. Our current study directly tested NT's role in maternal defense. Intracerebroventricular (icv) injections of NT significantly impaired defense in terms of time aggressive and number of attacks at all doses tested (0.05, 0.1, 1.0, and 3.0 μg). Other maternal behaviors, including pup retrieval, were unaltered following NT injections (0.05 μg) relative to vehicle, suggesting specificity of NT action on defense. Further, icv injections of the NT receptor 1 (NT1) antagonist, SR 48692 (30 μg), significantly elevated maternal aggression in terms of time aggressive and attack number. To understand where NT may regulate aggression, we examined Fos following injection of either 0.1 μg NT or vehicle. 13 of 26 brain regions examined exhibited significant Fos increases with NT, including regions expressing NT1 and previously implicated in maternal aggression, such as lateral septum, bed nucleus of stria terminalis, paraventricular nucleus, and central amygdala. Together, our results indicate that NT inversely regulates maternal aggression and provide the first direct evidence that lowering of NT signaling can be a mechanism for maternal aggression. To our knowledge, this is the first study to directly link NT to a social behavior. Keywordsfight; flight; maternal aggression; maternal defense; lactation; mice Neurotensin (NT) is a versatile neuropeptide that plays a role in analgesia (Dubuc et al., 1999, Sarret et al., 2005, hypothermia (Nemeroff et al., 1977, Martin et al., 1980, Remaury et al., 2002, and schizophrenia (Nemeroff, 1986, Kinkead and. NT acts most commonly via either NT receptor 1 (NT1) or receptor 2 (NT2) (Tanaka et al., 1990, Richard et al., 2001, Sarret et al., 2002, but it can also act via NT receptor 3, a sortilin receptor that internalizes the ligand (Mazella, 2001). NT and its receptors are highly conserved among mammals (Dobner, 2005). Although NT is expressed in and acts upon a number of areas critical for social behavior, including nucleus accumbens, lateral septum (LS), bed nucleus of stria terminalis (BNST), preoptic area, amygdala, and periaqueductal gray (Boudin et al., 1996, Binder et al., 2001a, Sarret et al., 2003, it has received almost no research attention regarding Corresponding Author: Stephen C. Gammie, 1117 W. Johnson St., Madison, WI 53706, Telephone: (608) Fax: (608) 262-9083, E-mail: scgammie@wisc.edu. Section Editor: Joan Morrell Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscrip...

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“…These subregions also differ with respect to relative distribution of certain neuropeptides such as cholecystokinin (Lanca et al, 1998) and in the density of some receptor populations including high affinity neurotensin receptors (Pickel et al, 2001). The differences between these two subregions may have functional significance with regard to their response to the presence of ethanol.…”

Section: Introductionmentioning

confidence: 99%

Deep brain stimulation of the nucleus accumbens reduces ethanol consumption in rats

Knapp

Tozier

Pak

et al. 2009

Pharmacology Biochemistry and Behavior

119

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Recent studies have shown that deep brain stimulation (DBS) of the nucleus accumbens (NAcc) has an inhibitory effect on drug-seeking behaviors including reinstatement responding for cocaine. The objective of the present study was to expand on these findings by assessing the effects of DBS on behaviors related to alcohol consumption. The specific aim of this study was to determine whether DBS delivered to either the shell or core of the NAcc would reduce ETOH intake in rats using a twobottle choice limited access procedure. Long Evans rats were induced to drink a 10% ethanol solution using a saccharin fading procedure. Bipolar electrodes were implanted bilaterally into either the core or shell of the NAcc. During testing animals received DBS 5 minutes prior to and during a 30-minute test session in which both ETOH and water bottles were accessible. Current was delivered at amplitudes ranging between 0 to 150 uA. ETOH consumption was significantly reduced from baseline levels at the 150 uA current for both shell and core electrode placements. A significant current effect was not found for water consumption for either site. These results provide evidence that DBS delivered either to the nucleus accumbens core or shell subregions can significantly reduce ethanol intake in the rat.

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High‐affinity neurotensin receptors in the rat nucleus accumbens: Subcellular targeting and relation to endogenous ligand

Cited by 37 publications

References 80 publications

Activation of neurotensin receptor type 1 attenuates locomotor activity

Activation of neurotensin receptor type 1 attenuates locomotor activity

Neurotensin inversely modulates maternal aggression

Deep brain stimulation of the nucleus accumbens reduces ethanol consumption in rats

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