Stimulation of food intake following opioid microinjection into the nucleus accumbens septi in rats

doi:10.1016/0196-9781(86)90083-5

Peptides

Volume 7, Issue 5, September–October 1986, Pages 711-716

https://doi.org/10.1016/0196-9781(86)90083-5 Get rights and content

Abstract

The involvement of opioid peptides in the regulation of food intake has been postulated. However, it is not known how they are involved in this regulation and which brain region is responsible for the mediation of their effects. We studied the effect of a microinjection of opioid agonists and antagonists into the nucleus accumbens septi (NAS) on the food intake in rats, as this area is known to be important for motivation. Male Wistar rats were implanted stereotaxically with guide cannulae. Rats were not allowed food prior to drug treatment and solutions (1 μl) were microinjected bilaterally. Food intake was measured throughout a 2 hr period after the drug injection. Infusions into the NAS of 2, 5 and 10 nmol of morphine, D-ala², D-Leu⁵-enkephalin (DADLE), and β-endorphin (βE), or of 5 and 10 nmol of α-neoendorphin (ANEO) induced a dose-dependent increase in the food intake. Dynorphin (DYN) also increased the food intake, but only at a 10 nmol dose. The new, highly selective delta agonist D-Pen^2,5-enkephalin (DPDPE) induced a dose-dependent increase in the food intake. Naloxone in doses of 2 and 10 nmol antagonized the increased food intake induced by morphine, βE, ANEO and DYN in a dose-dependent manner, but only partly antagonized the effect of DADLE on the food intake. The selective mu-receptor antagonist β-funaltrexamine (β-FNA), in a dose of 5 nmol completely blocked the increase in the food intake induced by morphine but not by DADLE. Our results indicate that stimulation of opiate receptors of the mu and delta rather than kappa-type within the NAS enhanced the food intake, therefore areas other than the lateral hypothalamus may be involved in the mechanism by which opioids increase the food intake.

References (47)

D.R. Brown et al.
Suppression of deprivation-induced food and water intake in rats and mice by naloxone
Pharmacol Biochem Behav
(1979)
K.J. Chang et al.
Multiple opiate receptors: Enkephalins and morphine bind to receptors of different specificity
J Biol Chem
(1979)
S.J. Cooper et al.
Effect of tifluadom on food consumption compared with chlordiazepoxide and kappa agonists in the rat
Neuropharmacology
(1985)
M.C. De Felipe et al.
Chronic antidepressant treatment increases enkephalin levels in nucleus accumbens and striatum of the rat
Eur J Pharmacol
(1985)
W. Fratta et al.
Distribution of β-endorphin and related peptides in the hypothalamus and pituitary
Neuroscience
(1979)
J. Garzón et al.
Endogenous opioid peptides: Comparative evaluation of their receptor affinities in the mouse brain
Life Sci
(1983)
N.E. Goeders et al.
Self-administration of methionine enkephalin into the nucleus accumbens
Pharmacol Biochem Behav
(1984)
L. Grandison et al.
Stimulation of food intake by muscimol and beta-endorphin
Neuropharmacology
(1977)
H.C. Jackson et al.
Are delta opioid receptor involved in the regulation of food and water intake?
Neuropharmacology
(1985)
K.W. Locke et al.
Effect of opiate antagonists and putative mu- and kappa-agonists on milk intake in rat and squirrel monkey
Pharmacol Biochem Behav
(1982)

J.D. Belluzzi et al.

Enkephalin may mediate euphoria and drive-reduction reward

Nature

(1977)

F. Bloom et al.

Neurons containing β-endorphin in rat brain exist separately from those containing enkephalin: Immunocytochemical studies

S.J. Cooper

Naloxone: effects on food and water consumption in the non-deprived and deprived rat

Psychopharmacology (Berlin)

(1980)

Cited by (95)

Role of the striatal dopamine, GABA and opioid systems in mediating feeding and fat intake
2022, Neuroscience and Biobehavioral Reviews
Food intake, which is a highly reinforcing behavior, provides nutrients required for survival in all animals. However, when fat and sugar consumption goes beyond the daily needs, it can favor obesity. The prevalence and severity of this health problem has been increasing with time. Besides covering nutrient and energy needs, food and in particular its highly palatable components, such as fats, also induce feelings of joy and pleasure. Experimental evidence supports a role of the striatal complex and of the mesolimbic dopamine system in both feeding and food-related reward processing, with the nucleus accumbens as a key target for reward or reinforcing-associated signaling during food intake behavior. In this review, we provide insights concerning the impact of feeding, including fat intake, on different types of receptors and neurotransmitters present in the striatal complex. Reciprocally, we also cover the evidence for a modulation of palatable food intake by different neurochemical systems in the striatal complex and in particular the nucleus accumbens, with a focus on dopamine, GABA and the opioid system.
Challenges and new opportunities for detecting endogenous opioid peptides in reward
2022, Addiction Neuroscience
The endogenous opioid peptide system, comprised of enkephalins, endorphins, dynorphins, and nociceptin, is a highly complex neurobiological system. Opioid peptides are derived from four precursor molecules and undergo several processing events yielding over 20 unique opioid peptides. This diversity together with low in vivo concentration and complex processing and release dynamics has challenged research into each peptide's unique function. Despite the subsequent challenges in detecting and quantifying opioid peptides in vivo, researchers have pioneered several techniques to directly or indirectly assay the roles of opioid peptides during behavioral manipulations. In this review, we describe the limitations of the traditional techniques used to study the role of endogenous opioid peptides in food and drug reward and bring focus to the wealth of new techniques to measure endogenous opioid peptides in reward processing.
Shifting motivational states: The effects of nucleus accumbens dopamine and opioid receptor activation on a modified effort-based choice task
2021, Behavioural Brain Research
The nucleus accumbens (NAc) is critical for regulating the appetitive and consummatory phases of motivated behavior. These experiments examined the effects of dopamine and opioid receptor manipulations within the NAc during an effort-based choice task that allowed for simultaneous assessment of both phases of motivation. Male Sprague-Dawley rats received bilateral guide cannulas targeting the NAc core and were tested in 1-hr sessions with free access to rat chow and the choice to work for sugar pellets on a progressive ratio 2 (PR2) reinforcement schedule. Individual groups of rats were tested following stimulation or blockade of NAc D1-like or D2-like receptors, stimulation of μ-, δ-, or κ-opioid receptors, or antagonism of opioid receptors. Behavior was examined under ad libitum conditions and following 23-h food restriction. NAc blockade of the D1-like receptors or stimulation of the D2 receptor reduced break point for earning sugar pellets; D2 receptor stimulation also modestly lowered chow intake. NAc μ-opioid receptor stimulation increased intake of the freely-available chow while simultaneously reducing break point for the sugar pellets. In non-restricted conditions, δ-opioid receptor stimulation increased both food intake and breakpoint. There were no effects of stimulating NAc D1 or κ receptors, nor did blocking D2 or opioid receptors affect task behavior. These data support prior literature linking dopamine to appetitive motivational processes, and suggest that μ- and δ-opioid receptors affect food-directed motivation differentially. Specifically, μ-opioid receptors shifted behavior towards consumption, and δ-opioid receptor enhanced both sugar-seeking and consumption of the pabulum chow when animals were not food restricted.
Beta and gamma synchronous oscillations in neural network activity in mice-induced by food deprivation
2019, Neuroscience Letters
Food deprivation is known to trigger hunger sensation and motivation to eat for energy replenishing. However, brain mechanisms associated with hunger and neural circuitries that mediate hunger driven responses remained to be investigated. To understand neural signaling of hunger, local field potentials (LFPs) in the lateral hypothalamus (LHa), nucleus accumbens (NAc), dorsal hippocampus (HP) and olfactory bulb (OB) and their interconnectivities were studied in freely moving adult male Albino mice during 18–20 h food deprivation and fed periods. Raw LFP signals were recorded and analyzed for mean values of spectral frequency power and coherence values. One-way repeated measures ANOVA revealed significant increases in spectral powers of beta and gamma frequency ranges induced by food deprivation in the LHa, HP, NAc but not OB. No change of spectral power in these brain regions was induced by food feeding. The analyses of coherent activity between brain regions also deliniated some distributed neural network activities correlated with hunger. In particular, coherent function indicated the increased beta and gamma phase synchrony between the pairs of LHa-HP and NAc-OB regions, and decreased gamma synchrony between the pairs of LHa-NAc and NAc-HP induced by food deprivation. It was found that plasma glucose level, locomotor count, travelled distance and time spent on moving were not altered by food deprivation. These results suggest that changes in LFP hallmarks in these brain regions were associated with hunger driven by negative energy balance.
Endogenous opioid modulation of food intake and body weight: Implications for opioid influences upon motivation and addiction
2019, Peptides
This review is part of a special issue dedicated to Opioid addiction, and examines the influential role of opioid peptides, opioid receptors and opiate drugs in mediating food intake and body weight control in rodents. This review postulates that opioid mediation of food intake was an example of “positive addictive” properties that provide motivational drives to maintain opioid-seeking behavior and that are not subject to the “negative addictive” properties associated with tolerance, dependence and withdrawal. Data demonstrate that opiate and opioid peptide agonists stimulate food intake through homeostatic activation of sensory, metabolic and energy-related In contrast, general, and particularly mu-selective, opioid receptor antagonists typically block these homeostatically-driven ingestive behaviors. Intake of palatable and hedonic food stimuli is inhibited by general, and particularly mu-selective, opioid receptor antagonists. The selectivity of specific opioid agonists to elicit food intake was confirmed through the use of opioid receptor antagonists and molecular knockdown (antisense) techniques incapacitating specific exons of opioid receptor genes. Further extensive evidence demonstrated that homeostatic and hedonic ingestive situations correspondingly altered the levels and expression of opioid peptides and opioid receptors. Opioid mediation of food intake was controlled by a distributed brain network intimately related to both the appetitive-consummatory sites implicated in food intake as well as sites intimately involved in reward and reinforcement. This emergent system appears to sustain the “positive addictive” properties providing motivational drives to maintain opioid-seeking behavior.
Whole-brain patterns of the presynaptic inputs and axonal projections of BDNF neurons in the paraventricular nucleus
2019, Journal of Genetics and Genomics
Brain-derived neurotrophic factor (BDNF) plays a crucial role in human obesity. Yet, the neural circuitry supporting the BDNF-mediated control of energy homeostasis remains largely undefined. To map key regions that might provide inputs to or receive inputs from the paraventricular nucleus (PVN) BDNF neurons, a key type of cells in regulating feeding and thermogenesis, we used rabies virus-based transsynaptic labeling and adeno-associated virus based anterograde tracing techniques to reveal their whole-brain distributions. We found that dozens of brain regions provide dense inputs to or receive dense inputs from PVN BDNF neurons, including several known weight control regions and several novel regions that might be functionally important for the BDNF-mediated regulation of energy homeostasis. Interestingly, several regions show very dense reciprocal connections with PVN BDNF neurons, including the lateral septum, the preoptic area, the ventromedial hypothalamic nucleus, the paraventricular thalamic nucleus, the zona incerta, the lateral parabrachial nucleus, the subiculum, the raphe magnus nucleus, and the raphe pallidus nucleus. These strong anatomical connections might be indicative of important functional connections. Therefore, we provide an outline of potential neural circuitry mediated by PVN BDNF neurons, which might be helpful to resolve the complex obesity network.

View all citing articles on Scopus

¹: A post-graduate student at the Department of Pharmacology, Mosul University, Mosul, Iraq; at present working for his Ph.D. Degree in the Institute of Pharmacology, Polish Academy of Sciences.

View full text

Stimulation of food intake following opioid microinjection into the nucleus accumbens septi in rats

Abstract

Pharmacol Biochem Behav

J Biol Chem

Neuropharmacology

Eur J Pharmacol

Neuroscience

Life Sci

Pharmacol Biochem Behav

Neuropharmacology

Neuropharmacology

Pharmacol Biochem Behav

Life Sci

Brain Res

Life Sci

Peptides

Brain Res

Life Sci

Eur J Pharmacol

Life Sci

Brain Res

Life Sci

Enkephalin may mediate euphoria and drive-reduction reward

Nature

Neurons containing β-endorphin in rat brain exist separately from those containing enkephalin: Immunocytochemical studies

Naloxone: effects on food and water consumption in the non-deprived and deprived rat

Psychopharmacology (Berlin)