Regional expression of c-fos in rat brain following stimulation of the ventral tegmental area

doi:10.1016/S0304-3940(96)13222-5

Neuroscience Letters

Volume 220, Issue 1, 6 December 1996, Pages 17-20

https://doi.org/10.1016/S0304-3940(96)13222-5 Get rights and content

Abstract

This study has investigated the effect of stimulating the region of origin of the mesolimbic dopaminergic system, the ventral tegmental area (VTA), with the substance P analogue DiMe-C7 on the regional expression of c-fos in the rat forebrain. We have previously shown this treatment produced a prolonged increase in blood pressure and heart rate which was mediated by both dopaminergic mechanisms and vasopressin release. Stimulation of the VTA resulted in increased levels of c-Fos immunostaining in several target regions of the mesolimbic dopaminergic system (such as the frontal cortex, olfactory tubercle, islands of Calleja and amygdala), with the notable exception of the nucleus accumbens. A marked increase in c-fos expression was also found in the supraoptic nucleus but not the paraventricular nucleus in the hypothalamus. These results support a role for a number of target areas of the mesolimbic dopaminergic system and vasopressin release in the increase in blood pressure and heart rate produced by stimulation of the VTA.

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Mechanism of the cardiovascular effects of the GABA<inf>A</inf> receptors of the ventral tegmental area of the rat brain
2015, Neuroscience Letters
Citation Excerpt :
Stimulation of dopaminergic and non-dopaminergic cells in the ventral midbrain produced a marked increase in the expression of the proto-oncogene c-fos in the supraoptic nucleus and a significant increase in plasma vasopressin levels, suggesting the activation of vasopressinergic neurons in this area [11]. Microinjection of substance P analogue DiMe-C7 into the VTA produced an increase in dopamine release [21] and increased arterial pressure which is mediated by release of vasopressin into circulation and marked cellular activity in supraoptic nucleus of the hypothalamus, a major source of pituitary vasopressin [11,22,23]. Nevertheless, no direct input from the VTA to either PVN or SON has been described [24,25], suggesting that the effect of GABAergic neurons of the VTA on vasopressin release may be mediated by an indirect neuronal pathway.
The ventral tegmental area (VTA) contains GABA terminals involved in the regulation of the cardiovascular system. Previously, we demonstrated that blocking GABA_A but not GABA_B receptors produced a pressor response accompanied by marked bradycardia. This study was performed to find the possible mechanisms involved in these responses by blocking ganglionic nicotinic receptors, peripheral muscarinic receptors or peripheral V₁ vasopressin receptors.
Experiments were performed on urethane anesthetized male Wistar rats. Drugs were microinjected unilaterally into the VTA (100 nl). The average changes in mean arterial pressure (MAP) and heart rate (HR) were compared between pre- and post-treatment using paired t-test.
Injection of bicuculline methiodide (BMI), a GABA_A antagonist, into the VTA caused a significant increase in MAP and a decrease in HR. Administration (i.v.) of the nicotinic receptor blocker, hexamethonium, enhanced the pressor response but abolished the bradycardic response to BMI, which ruled out involvement of the sympathetic nervous system. Blockade of the peripheral muscarinic receptors by homatropine (i.v.) abolished the bradycardic effect of BMI, but had no effect on the pressor response, indicating that bradycardia was produced by the parasympathetic outflow to the heart. Both the pressor and bradycardic responses to BMI were blocked by V₁ receptor antagonist (i.v.), indicating that administration of BMI in the VTA disinhibited the release of vasopressin into the circulation.
In conclusion, we demonstrated that GABAergic mechanism of the VTA exerts a tonic inhibition on vasopressin release through activation of GABA_A receptors. The sympathetic system is not involved in the decrease of blood pressure by GABA of the VTA.
Morphine self-administration into the lateral septum depends on dopaminergic mechanisms: Evidence from pharmacology and Fos neuroimaging
2007, Behavioural Brain Research
Mice self-administer morphine into the lateral septum (LS), but the neuronal connections underlying this behaviour remain unknown. The present study tested whether the acquisition of intra-LS morphine self-administration depends on dopaminergic mechanisms. Mice were allowed to self-inject morphine (5 or 20 ng/50 nl) or vehicle directly into the LS using a spatial discrimination Y-maze task. Fos imaging was used to evaluate neuronal activation in cerebral structures directly connected to the LS or belonging to the dopaminergic system. The involvement of dopaminergic and opioidergic mechanisms was assessed by pre-treating naive mice peripherally with the D1 antagonist SCH23390, the D2/D3 antagonist sulpiride or the opiate antagonist naloxone before daily self-administration sessions. Mice acquired self-administration behaviour for intra-LS morphine that was associated with increased Fos expression in the ventral tegmental area (VTA), dorsal and ventral striatum and prefrontal cortex. Pre-treating animals with naloxone, SCH23390 or sulpiride completely prevented them from acquiring intra-LS morphine self-administration. All three antagonists consistently blocked Fos expression in the prefrontal cortex, but not in the VTA and striatum. Taken together, our results show that morphine self-administration into the LS depends on dopaminergic (D1 and D2/D3) and opioidergic mechanisms. Furthermore, they suggest that opioid peptides released in the LS could participate in regulating the activity of mesotegmental dopaminergic neurons.
Central nucleus of the amygdala and the effects of alcohol and alcohol-drinking behavior in rodents
2002, Pharmacology Biochemistry and Behavior
This article will review key literature on the effects of alcohol on the amygdala and the involvement of the amygdala in regulating alcohol drinking in mice and rats. Special emphasis will be placed on the central nucleus of the amygdala (CeA) because this nucleus is a major component of the extended amygdala, which has been implicated in regulating alcohol-drinking behavior. Immunocytochemical and in situ hybridization studies indicate that acute high-dose ethanol administration increases c-fos expression in GABAergic neurons within the CeA of the rat, suggesting activation of these neurons by ethanol. A similar high-dose (4 g/kg ethanol) effect on c-fos expression in the CeA of C57 mice was also observed, whereas the DBA mice showed increased c-fos expression in the CeA in the dose range of 1.25–4.0 g/kg. Studies with DBA×C57 F2 intercross mice suggest that there may be a relationship between the neuronal activating effects of ethanol in the CeA and the locomotor stimulating effects of ethanol. Studies with rats examining the effects of acute ethanol or chronic alcohol drinking on local cerebral glucose utilization (LCGU) rates (as a measure of synaptic activity) indicated that (a) acute ethanol (0.25–2.0 g/kg) had little effect on LCGU rates in the CeA; (b) basal LCGU rates were reduced in the CeA as a result of chronic alcohol drinking; and (c) oral self-administration of ethanol increased LCGU values within the CeA. Microdialysis studies demonstrated that acute ethanol (2 g/kg) injection increased dopamine (DA) and serotonin (5-HT) release in the CeA. Microinjection studies indicate that GABA_A receptors within the CeA are involved in oral ethanol self-administration. Overall, the findings from the various studies support a role for the CeA in mediating the stimulating actions of alcohol in mice and regulating alcohol-drinking behavior in mice and rats.
A functional interaction between the mesolimbic dopamine system and vasopressin release in the regulation of blood pressure in conscious rats
1997, Neuroscience
The aim of the present study was to further characterize the involvement of the mesolimbic dopamine system in central blood pressure regulation, with particular emphasis on the interaction of this system with the effects of circulating vasopressin. In conscious rats we stimulated the release of endogenous dopamine from mesolimbic/mesocortical terminals by administration of the substance P analogue DiMe-C7 ([pGlu⁵, MePhe⁸, Sar⁹]-Substance P_5–11; 10 nmol) into the ventral tegmental area. Chemical stimulation of the ventral tegmental area resulted in a significant increase in blood pressure and heart rate. These effects were prevented by either bilateral electrolytic lesions of the hypothalamic supraoptic nucleus or by systemic pretreatment with the dopamine D₂ receptor antagonist raclopride (0.5 mg/kg). Stimulation of the ventral tegmental area also produced a marked increase in the expression of the proto-oncogene c-fos in the supraoptic nucleus and a significant increase in plasma vasopressin levels, suggesting activation of vasopressinergic neurons in this nucleus. However, this effect of stimulation of the ventral tegmental area was not significantly inhibited by pretreatment with raclopride.
We suggest that the effects on blood pressure and heart rate of stimulation of the ventral midbrain by micro-injection of DiMe-C7 are the result of combined activation of both dopaminergic and non-dopaminergic cell bodies in this region. Stimulation of non-dopaminergic cells in the ventral midbrain may induce a moderate increase in plasma vasopressin levels by activation of the supraoptic nucleus. An additional stimulation of dopaminergic cells in the ventral midbrain allows the increase in circulating vasopressin levels to become manifest as a pressor response, possibly by inhibition of vasopressin-induced facilitation of baroreflex responses.
Whole-body bioelectrical impedance analysis in assessing upper-limb lymphedema after breast cancer therapy
2013, Anticancer Research
Whole-body versus segmental bioelectrical impedance analysis in patients with edema of the upper limb after breast cancer treatment
2013, Anticancer Research

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^☆: This study was supported by a NH and MRC block grant to the Baker Medical Research Institute.

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Neuroscience Letters

Abstract

References (28)

Neurochemical consequences following injection of the substance P analogue, DiMe-C7 into the rat ventral tegmental area

Pharmacol. Biochem. Behav.

Cardiovascular and single unit responses elicited by stimulation of the islands of Calleja and by changes in arterial pressure

Brain Res.

Pressor responses to electrical and chemical stimulation of the rat brain A10 dopaminergic system

Neurosci. Lett.

Stimulation of the rat mesolimbic dopaminergic system produces a pressor response which is mediated by dopamine D-1 and D-2 receptor activation and the release of vasopressin

Brain Res.

Selective activation of mesolimbic and mesocortical dopamine metabolism in rat brain by infusion of a stable substance P analogue into the ventral tegmental area

Brain Res.

c-Fos expression in brain in response to hypotension and hypertension in conscious rats

J. Autonomic Nerv. Syst.

Dopaminergic modulation of bulbofugal projections in the rat olfactory tubercle

Am. J. Otolaryngol.

Modulation of dopaminergic activity in the nucleus accumbens following facilitation or blockade of the dopaminergic transmission in the amygdala: a study by in vivo differential pulse voltammetry

Brain Res.

Intravenous angiotensin II induces Fos-immunoreactivity in circumventricular organs of the lamina terminalis

Brain Res.

Expression of c-fos protein in rat brain after electrical stimulation of the aortic depressor nerve

Brain Res.

Ventral tegmental (A10) system: neurobiology. 1, Anatomy and connectivity

Brain Res. Rev.

Regulation of signalling pathways to the nucleus by dopaminergic receptors

Cell Signalling

Blockade of GABA-A receptors in the region of the basolateral amygdala of rats elicits increases in heart rate and blood pressure

Brain Res.

In the rat medial nucleus accumbens, hippocampal and catecholaminergic terminals converge on spiny neurons and are in apposition to each other

Brain Res.

Cited by (13)

Mechanism of the cardiovascular effects of the GABA<inf>A</inf> receptors of the ventral tegmental area of the rat brain

Morphine self-administration into the lateral septum depends on dopaminergic mechanisms: Evidence from pharmacology and Fos neuroimaging

Central nucleus of the amygdala and the effects of alcohol and alcohol-drinking behavior in rodents

A functional interaction between the mesolimbic dopamine system and vasopressin release in the regulation of blood pressure in conscious rats

Whole-body bioelectrical impedance analysis in assessing upper-limb lymphedema after breast cancer therapy

Whole-body versus segmental bioelectrical impedance analysis in patients with edema of the upper limb after breast cancer treatment

Regional expression of c-fos in rat brain following stimulation of the ventral tegmental area☆

Abstract

Pharmacol. Biochem. Behav.

Brain Res.

Neurosci. Lett.

Brain Res.

Brain Res.

J. Autonomic Nerv. Syst.

Am. J. Otolaryngol.

Brain Res.

Brain Res.

Brain Res.

Brain Res. Rev.

Cell Signalling

Brain Res.

Brain Res.