Increase in spontaneous motor activity following infusion of neurotensin into the ventral tegmental area

doi:10.1016/0006-8993(81)91016-7

Brain Research

Volume 229, Issue 2, 21 December 1981, Pages 525-529

https://doi.org/10.1016/0006-8993(81)91016-7 Get rights and content

Abstract

Microinjection of neurotensin (NT) into the ventral tegmental area (VTA) of the rat produced a dose-dependent increase in spontaneous motor activity. The NT-induced hyperactivity consisted of an increase in exploratory behaviors, such as locomotion, rearing and sniffing, and a decrease in sleep or resting. The structural specificity of this response was demonstrated by microinjecting NT analogues and endogenous neuropeptides into the VTA. The fact that high levels of immunoreactive NT have been demonstrated in the VTA indicates that the observed behavioral effects may reflect an underlying physiological action by endogenous NT.

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Pivotal role of the ventral tegmental area in spontaneous motor activity and concomitant cardiovascular responses in decerebrate rats
2020, Brain Research
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In the rostroventral midbrain, a putative candidate for the synchronized motor and cardiovascular responses is the VTA. Chemical stimulation of the VTA can cause or increase motor activity (Mogenson et al., 1979; Kalivas et al., 1981) and change the cardiovascular variables (Cornish and van den Buuse, 1995). Matsukawa and colleagues demonstrated that in the decerebrate rats, the VTA stimulation by an antagonist of GABAergic type A receptors (bicuculline methochloride) caused rhythmic and synchronous bursts of the tibial motor nerve and the renal sympathetic nerve as well as increases in HR, MAP, and muscle blood flow (Nakamoto et al., 2011; Matsukawa et al., 2011).
Central command, a feedforward signal from higher brain centers, regulates the cardiovascular system in association with exercise. Previous evidence suggests that nucleus (or nuclei) around the midbrain may contribute to generating spontaneous motor activity and concomitant cardiovascular responses. To examine which area within the midbrain is important for the spontaneous and synchronized responses, 18 rats were decerebrated at three levels (pre-midbrain, rostroventral midbrain, and caudal midbrain levels) and paralyzed with a neuromuscular blocker. Individual brain sections showed decerebration rostral to the pre-collicular level in the pre-midbrain preparation and, additionally, removal of the periaqueductal gray in the rostroventral midbrain preparation, and decerebration around the midcollicular level in the caudal midbrain preparation. Spontaneous motor activity occurred at frequency of 69 ± 27 times/h and accompanied increases in heart rate (by 15 ± 4 beats/min) and mean arterial blood pressure (by 54 ± 4 mmHg) in the pre-midbrain preparation. Similar motor and cardiovascular responses took place in the rostroventral midbrain preparation, while such responses hardly occurred in the caudal midbrain preparation. We next examined whether injection of a GABAergic receptor agonist (muscimol) in the ventral tegmental area (VTA) inhibits the spontaneous motor and cardiovascular responses in 6 pre-midbrain preparations. The occurrence of spontaneous motor activity and concomitant cardiovascular responses was inhibited clearly (P < 0.05) by injection of muscimol, but not saline. It is concluded that the VTA plays a pivotal role in the spontaneous and synchronized activation of the motor and cardiovascular systems in decerebrate rats.
The neural circuitry supporting successful spatial navigation despite variable movement speeds
2020, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
This putative functional anatomy includes a direct MSDB-to-VTA projection (Fuhrmann et al., 2015; Geisler and Wise, 2008) and a hippocampal-originating projection that works through first the lateral septum and next the lateral hypothalamus before reaching the VTA (Bender et al., 2015; Geisler and Wise, 2008). All of these regions have been shown to contain rate codes for speed (Zhou et al., 1999; Puryear et al., 2010; Wang and Tsien, 2011; Bender et al., 2015) and to modulate locomotion upon stimulation (Kalivas et al., 1981; Parker and Sinnamon, 1983; Christopher and Butter, 1968; Patterson et al., 2015; Bender et al., 2015). Moreover, the VTA makes functional connections with the nucleus accumbens (NAc), striatum, and motor cortex (Mogenson et al., 1980; Hosp et al., 2011; Kunori et al., 2014; Beier et al., 2015), providing access to canonical locomotive control circuitry.
Ants who have successfully navigated the long distance between their foraging spot and their nest dozens of times will drastically overshoot their destination if the size of their legs is doubled by the addition of stilts. This observation reflects a navigational strategy called path integration, a strategy also utilized by mammals. Path integration necessitates that animals keep track of their movement speed and use it to precisely and instantly modify where they think they are and where they want to go. Here we review the neural circuitry that has evolved to integrate speed and space. We start with the rate and temporal codes for speed in the hippocampus and work backwards towards the motor and sensory systems. We highlight the need for experiments designed to differentiate the respective contributions of motor efference copy versus sensory inputs. In particular, we discuss the importance of high-resolution tracking of the latency of speed-encoding as a precise way to disentangle the sensory versus motor computations that enable successful spatial navigation at very different speeds.
Determination of neurotensin projections to the ventral tegmental area in mice
2018, Neuropeptides
Citation Excerpt :
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). Intriguingly, many of these behavioral effects are specific to the VTA because Nts administration outside of the VTA elicits different effects.
Pharmacologic treatment with the neuropeptide neurotensin (Nts) modifies motivated behaviors such as feeding, locomotor activity, and reproduction. Dopamine (DA) neurons of the ventral tegmental area (VTA) control these behaviors, and Nts directly modulates the activity of DA neurons via Nts receptor-1. While Nts sources to the VTA have been described in starlings and rats, the endogenous sources of Nts to the VTA of mice remain incompletely understood, impeding determination of which Nts circuits orchestrate specific behaviors in this model. To overcome this obstacle we injected the retrograde tracer Fluoro-Gold into the VTA of mice that express GFP in Nts neurons. Identification of GFP-Nts cells that accumulate Fluoro-Gold revealed the Nts afferents to the VTA in mice. Similar to rats, most Nts afferents to the VTA of mice arise from the medial and lateral preoptic areas (POA) and the lateral hypothalamic area (LHA), brain regions that are critical for coordination of feeding and reproduction. Additionally, the VTA receives dense input from Nts neurons in the nucleus accumbens shell (NAsh) of mice, and minor Nts projections from the amygdala and periaqueductal gray area. Collectively, our data reveal multiple populations of Nts neurons that provide direct afferents to the VTA and which may regulate specific aspects of motivated behavior. This work lays the foundation for understanding endogenous Nts actions in the VTA, and how circuit-specific Nts modulation may be useful to correct motivational and affective deficits in neuropsychiatric disease.
Substance P and neurotensin in the limbic system: Their roles in reinforcement and memory consolidation
2018, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
The summary of central effects of NT can be seen in Table 2. NT microinjection into the VTA causes hyperactivity, i.e. increases locomotion, rearing and sniffing, additionally, it decreases sleep and resting (Kalivas et al., 1983; Kalivas et al., 1981). NT by itself does not influence the general activity in the NAC (Kalivas et al., 1983) and in the VP (Ollmann et al., 2015b; Torregrossa and Kalivas, 2008), however, it shows a tendency to increase cocaine-induced locomotion (Torregrossa and Kalivas, 2008).
Substance P (SP) and neurotensin (NT) are neuropeptides isolated in the periphery and in the central nervous system. They are involved in various regulatory processes in the gastrointestinal tract, in the circulatory and respiratory systems, kidney and endocrine system. In addition to the peripheral effects, SP and NT act as neurotransmitters and neuromodulators in the central nervous system, regulating various behavioural actions, such as general and motor activity, pain, food and water intake, anxiety, reward/reinforcement and memory consolidation. In the limbic system SPergic and NTergic pathways, terminals and related receptors have been identified. According to several data of literature and to our recently published results, SP and NT have rewarding/reinforcing effects and facilitate memory consolidation in various limbic regions. In this report evidences are provided about the interaction of these neuropeptides with dopaminergic and acetylcholinergic systems. A hypothesis is presented that rewarding/reinforcing effects of SP and NT develop by modulating the mesencephalic dopaminergic system, while their mnemonic effects are mediated via the mesencephalic dopaminergic and the basal forebrain cholinergic systems.
Locomotion, Theta Oscillations, and the Speed-Correlated Firing of Hippocampal Neurons Are Controlled by a Medial Septal Glutamatergic Circuit
2015, Neuron
Citation Excerpt :
1) The firing rate of VTA non-dopaminergic and dopaminergic neurons strongly increases during the initiation of locomotion (Lee et al., 2001; Wang and Tsien, 2011) and the neuronal activity correlates with locomotion speed (Puryear et al., 2010; Wang and Tsien, 2011). ( 2) Electrical stimulation of VTA reliably initiates locomotion (Kalivas et al., 1981; Parker and Sinnamon, 1983). ( 3) The MSDB directly projects to VTA via VGluT2-positive axons (Geisler and Wise, 2008), a projection that was confirmed by axonal tracing in the present study. (
Before the onset of locomotion, the hippocampus undergoes a transition into an activity-state specialized for the processing of spatially related input. This brain-state transition is associated with increased firing rates of CA1 pyramidal neurons and the occurrence of theta oscillations, which both correlate with locomotion velocity. However, the neural circuit by which locomotor activity is linked to hippocampal oscillations and neuronal firing rates is unresolved. Here we reveal a septo-hippocampal circuit mediated by glutamatergic (VGluT2⁺) neurons that is activated before locomotion onset and that controls the initiation and velocity of locomotion as well as the entrainment of theta oscillations. Moreover, via septo-hippocampal projections onto alveus/oriens interneurons, this circuit regulates feedforward inhibition of Schaffer collateral and perforant path input to CA1 pyramidal neurons in a locomotion-dependent manner. With higher locomotion speed, the increased activity of medial septal VGluT2 neurons is translated into increased axo-somatic depolarization and higher firing rates of CA1 pyramidal neurons.
The role of neurotensin in positive reinforcement in the rat central nucleus of amygdala
2010, Behavioural Brain Research
In the central nervous system neurotensin (NT) acts as a neurotransmitter and neuromodulator. It was shown that NT has positive reinforcing effects after its direct microinjection into the ventral tegmental area. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, regulation of feeding, anxiety and emotional behavior. By means of immunohistochemical and radioimmune methods it was shown that the amygdaloid body is relatively rich in NT immunoreactive elements and NT receptors.
The aim of our study was to examine the possible effects of NT on reinforcement and anxiety in the CeA. In conditioned place preference test male Wistar rats were microinjected bilaterally with 100 or 250 ng NT in volume of 0.4 μl or 35 ng neurotensin receptor 1 (NTS1) antagonist SR 48692 alone, or NTS1 antagonist 15 min before 100 ng NT treatment. Hundred or 250 ng NT significantly increased the time rats spent in the treatment quadrant. Prior treatment with the non-peptide NTS1 antagonist blocked the effects of NT. Antagonist itself did not influence the reinforcing effect. In elevated plus maze test we did not find differences among the groups as far as the anxiety index (time spent on the open arms) was concerned. Our results suggest that in the rat ACE NT has positive reinforcing effects. We clarified that NTS1s are involved in this action. It was also shown that NT does not influence anxiety behavior.

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Increase in spontaneous motor activity following infusion of neurotensin into the ventral tegmental area

Abstract

Europ. J. Pharmacol.

Brain Res. Bull.

Neuropharmacology

Trends Neurosci.

Brain Research

Brain Research

Role of monoamine neural pathways ind-amphetamine and methylphenidate-induced locomotor activity

Stimulant effects of enkephalin microinjection into the dopaminergic A10 area

Nature (Lond.)

Multiple comparisons among means

J. Am. stat. Ass.