Neurotensin and cholecystokinin microinjected into the ventral tegmental area modulate microdialysate concentrations of dopamine and metabolites in the posterior nucleus accumbens

Laitinen, Kirsti; Crawley, Jacqueline N.; Mefford, Ivan N.; Witte, Ph. De

doi:10.1016/0006-8993(90)91511-e

Cited by 73 publications

(25 citation statements)

References 35 publications

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“…Locomotion elicited by stimulating (or disinhibiting) the LPO and certain adjacent forebrain areas such as the ventral pallidum (see Zahm et al, 2014) is suppressed by systemic injections of dopamine antagonists Johnson et al, 1996;Zahm et al, 2011) and by infusion of dopamine antagonists directly into the Acb Johnson et al, 1996), indicating that the expression of this behavior is dependent upon intact mesoaccumbal dopaminergic neurotransmission. LPO-elicited locomotor activation is also suppressed by bilateral infusions into the VTA of an antagonist to the neurotensin 1 receptor (Reynolds et al, 2006), which, in the midbrain, is selectively enriched on dopamine neurons (Quirion et al, 1985;Woulfe and Beaudet, 1989;Bayer et al, 1991) and excites them (Seutin et al, 1989;Shi and Bunney, 1991;Litwin and Goldstein, 1994;Sotty et al, 2000;Werkman et al, 2000), causing dopamine release in the Acb (Blaha et al, 1990;Seutin et al, 1989;Kalivas and Duffy, 1990;Laitinen et al, 1990;Sotty et al, 2000), which further implicates impairment specifically of the VTA-Acb dopaminergic pathway as a critical impediment to locomotor activation. Alternatively, locomotion elicited by administration of psychostimulant drugs, such as D-amphetamine, which increase the levels of dopamine in the Acb, is suppressed by infusion of muscimol into the LPO and ventral pallidum (Austin and Kalivas, 1989;Zahm, unpublished observations), indicating that co-activation (or disinhibition) of the LPO and mesoaccumbal dopaminergic neurons is essential to locomotor activation, as also must be, presumably, downstream projections to motor effectors (Mogenson et al, 1985;Holstege, 1991).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Locomotor Activation by the Rostromedial Tegmental Nucleus

Lavezzi

Parsley

Zahm

2014

Neuropsychopharmacol

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The rostromedial tegmental nucleus (RMTg) is a strong inhibitor of dopamine neurons in the ventral tegmental area (VTA) reported to influence neurobiological and behavioral responses to reward omission, aversive and fear-eliciting stimuli, and certain drugs of abuse. Insofar as previous studies implicate ventral mesencephalic dopamine neurons as an essential component of locomotor activation, we hypothesized that the RMTg also should modulate locomotion activation. We observed that bilateral infusions into the RMTg of the gamma-aminobutyric acid A (GABA A ) agonist, muscimol, indeed activate locomotion. Alternatively, bilateral RMTg infusions of the GABA A receptor antagonist, bicuculline, suppress robust activations of locomotion elicited in two distinct ways: (1) by disinhibitory stimulation of neurons in the lateral preoptic area and (2) by return of rats to an environment previously paired with amphetamine administration. The possibility that suppressive locomotor effects of RMTg bicuculline infusions were due to unintended spread of drug to the nearby VTA was falsified by a control experiment showing that bilateral infusions of bicuculline into the VTA produce activation rather than suppression of locomotion. These results objectively implicate the RMTg in the regulation of locomotor activation. The effect is important because much evidence reported in the literature suggests that locomotor activation can be an involuntary behavioral expression of expectation and/or want without which the willingness to execute adaptive behaviors is impaired.

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Section: Discussionmentioning

confidence: 99%

Modulation of Locomotor Activation by the Rostromedial Tegmental Nucleus

Lavezzi

Parsley

Zahm

2014

Neuropsychopharmacol

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“…This transporter-mediated DA release, which is independent of impulse flow (Westerink et al, 1987;Carboni et al, 1989), strongly activates a DA inhibitory feedback mechanism and masks non-DA excitatory effects on mesolimbic DA neurons (Shi et al, 2000). Thus, amphetamine-induced DA release bypasses additional control by VTA inputs, so that the VTA NTstimulating effect on DA release in the NAC (Laitinen et al, 1990;Sotty et al, 1998) and on locomotor activity (Bauco and Rompré, 2003) might be ineffective under amphetamine exposure. Altogether, our results suggest that NT-receptor activation within the VTA may promote intracellular events that appear insufficient to affect the acute response to amphetamine but may lead or contribute in the long-term to behavioral sensitization.…”

Section: Discussionmentioning

confidence: 99%

“…When injected into the VTA, NT produces effects similar to those of systemically injected psychostimulants, such as increased motor activity (Kalivas et al, 1983) and elevated extracellular DA levels in the NAC (Kalivas and Duffy, 1990;Laitinen et al, 1990;Sotty et al, 1998). However, when injected into the NAC, NT has an opposite effect on psychostimulant-induced behaviors, attenuating the locomotion produced by systemic amphetamine or cocaine (Ervin et al, 1981;Robledo et al, 1993;Steinberg et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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

Panayi

Colussi-Mas

Lambás‐Señas

et al. 2004

Neuropsychopharmacol

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Studies showing psychostimulant-like effects of exogenous neurotensin (NT) infused into the ventral tegmental area (VTA) prompted us to examine the role in the VTA of the endogenous NT in behavioral sensitization to amphetamine. Rats were sensitized to amphetamine by means of a subcutaneous amphetamine (1 mg/kg) injection, and the same dose was injected 7 days later to evaluate the expression of sensitization. The highly selective NT-receptor antagonist SR 142948A was injected into the VTA prior to the first and/or second amphetamine administration. SR 142948A (5 pmol/side) given before the first amphetamine exposure prevented the induction of behavioral sensitization, but did not alter the acute response to amphetamine. SR 142948A given with the second amphetamine administration did not affect the expression of behavioral sensitization. In contrast to administration into the VTA, intraperitoneal administration of SR 142948A (0.03, 0.1, or 0.3 mg/kg) had no detectable effect on the induction of amphetamine sensitization. These results suggest that activation of VTA NT receptors by endogenous NT may contribute to the neuroadaptations underlying behavioral sensitization to amphetamine.

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“…Indeed, NT has been shown to co-exist with DA in a subset of mesencephalic neurons that project to the NAC and mPFC (Hökfelt et al 1984; Kalivas and Miller 1984;Seroogy et al 1987;Studler et al 1988; Bayer et al 1991) and to be coreleased with DA following psychostimulant administration (During et al 1992; Hertel et al 1996). Moreover, the injection of NT into the VTA produces psychostimulant-like behavioral and neurochemical activation effects such as increased locomotor activity and rearing (Kalivas et al 1983; Cador et al 1985) and enhanced extracellular levels of DA in the NAC (Kalivas and Duffy 1990;Laitinen et al 1990;Sotty et al 1998). Interestingly, repeated injection of NT into the VTA leads to a behavioral and neurochemical sensitization (Kalivas and Taylor 1985; Elliott and Nemeroff 1986; Kalivas and Duffy 1990).…”

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confidence: 99%

Chronic Blockade of Neurotensin Receptors Strongly Reduces Sensitized, but Not Acute, Behavioral Response to D-amphetamine

Panayi

Dorso

Lambás‐Señas

et al. 2002

Neuropsychopharmacology

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This study investigated the effect of a chronic blockade of neurotensin (NT) receptors on the sensitized behavioral response to amphetamine using a nonpeptide NT receptor antagonist, SR 48692. Rats received four injections of D-amphetamine (0.5 or 1 mg/kg, IP) every other day (day 1, 3, 5 and 7) and were then challenged with the same dose of amphetamine after a 6-day withdrawal (day 14) to establish the presence of locomotor sensitization. Daily administration of SR 48692 (1 mg/kg, IP) throughout the amphetamine regimen (day 1 to day 14) almost completely blocked the sensitized locomotor response to amphetamine without affecting stereotyped behaviors (experiment 1). The decreased amphetamine-induced sensitization in chronically SR 48692-treated rats did not appear to result from an influence on basal locomotor activity, as chronic SR 48692 treatment did not modify the spontaneous locomotor activity developed in response to mild stresses (experiment 2). Moreover, we showed that chronic pretreatment with SR 48692 (1 mg/kg, 14 daily IP injections) had no effect on the locomotor activation induced by a single IP administration of amphetamine (experiment 3). These data suggest that a sustained blockade of NTRepeated intermittent administration of psychostimulants, such as amphetamine and cocaine, leads to a progressive enhancement of their behavioral stimulant effects, as well as a long-lasting hyperreactivity in response to environmental or pharmacological challenges (Antelman et al. 1980;Kalivas and Stewart 1991). This phenomenon, termed behavioral sensitization, is considered as a useful animal model for drug-induced psychosis and drug craving in humans (Robinson and Becker 1986;Robinson and Berridge 1993;Lieberman et al. 1997;Laruelle 2000).The mesoaccumbens dopaminergic (DA) system, which originates within the ventral tegmental area (VTA) and projects to the nucleus accumbens (NAC), plays an important role in the behavioral sensitization to psychostimulants. Thus, repeated injections of am- phetamine into the VTA produce sensitized locomotor responses to systemic injections of amphetamine, cocaine and morphine. In contrast, although amphetamine produces locomotor stimulation upon acute injection into the NAC, repeated intra-NAC injections do not lead to sensitization (Kalivas and Weber 1988;Vezina and Stewart 1990; Hooks et al. 1992; Cador et al. 1995). Other studies have established that the mechanisms leading to the induction of sensitization require the action of DA, somatodendritically released by amphetamine, on D1 receptors in the VTA whereas DA release in the NAC appears as the prime event for the expression of behavioral sensitization (Vezina 1993(Vezina , 1996Pierce and Kalivas 1997a). However, recent studies support the view that the neural underpinnings of behavioral sensitization implicate additional limbic areas and neurotransmitters such as the medial prefrontal cortex (mPFC) and its glutamatergic components (Wolf 1998; Cador et al. 1999) or the ventral pallidum and its GABAergic components (Pier...

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Neurotensin and cholecystokinin microinjected into the ventral tegmental area modulate microdialysate concentrations of dopamine and metabolites in the posterior nucleus accumbens

Cited by 73 publications

References 35 publications

Modulation of Locomotor Activation by the Rostromedial Tegmental Nucleus

Modulation of Locomotor Activation by the Rostromedial Tegmental Nucleus

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

Chronic Blockade of Neurotensin Receptors Strongly Reduces Sensitized, but Not Acute, Behavioral Response to D-amphetamine

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