Discriminative stimuli are sufficient for incubation of cocaine craving

In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency (‘incubate’) over time. Animal models of incubation may help develop treatments to prevent relapse, but these models have ubiquitously focused on the role of conditioned stimuli (CSs) signaling drug delivery. Discriminative stimuli (DSs) are unique in that they exert stimulus-control over both drug taking and drug seeking behavior and are difficult to extinguish. For this reason, incubation of the excitatory effects of DSs that signal drug availability, not yet examined in preclinical studies, could be relevant to relapse prevention. We trained rats to self-administer cocaine (or palatable food) under DS control, then investigated DS-controlled incubation of craving, in the absence of drug-paired CSs. DS-controlled cocaine (but not palatable food) seeking incubated over 60 days of abstinence and persisted up to 300 days. Understanding the neural mechanisms of this DS-controlled incubation holds promise for drug relapse treatments.

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Incubation of discriminative stimulus-controlled cocaine craving: An animal model relevant to relapse prevention

10.1101/494070 ◽

2018 ◽

Author(s):

Rajtarun Madangopal ◽

Brendan J Tunstall ◽

Lauren E Komer ◽

Sophia J Weber ◽

Jennifer K Hoots ◽

...

Keyword(s):

Relapse Prevention ◽

Neural Mechanisms ◽

Drug Addicts ◽

Preclinical Studies ◽

Palatable Food ◽

Cocaine Craving ◽

Food Seeking ◽

Over Time ◽

Time Animal

In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency ('incubate') over time. Animal models of incubation may help develop treatments to prevent relapse, but these models have ubiquitously focused on the role of conditioned stimuli (CSs) signaling drug delivery. From a translational perspective this is problematic because people encounter these stimuli only during or after relapse. For this reason, incubation in response to discriminative stimuli (DSs) that signal drug availability before relapse, not yet examined in preclinical studies, could be more relevant to relapse prevention. We trained rats to self-administer cocaine (or palatable food) under DS control, then investigated DS-controlled incubation of craving, in the absence of drug-paired CSs. DS-controlled cocaine (but not palatable food) seeking incubated over 60 days of abstinence and persisted up to 300 days. Understanding the neural mechanisms of this DS-controlled incubation holds significant promise for drug relapse treatments.

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Changes in activity rates in the cherry shrimp Neocaridina davidi Bouvier, 1904 (Decapoda: Caridea: Atyidae) in response to concentrations of neuropeptides and glucose

Journal of Crustacean Biology ◽

10.1093/jcbiol/ruz059 ◽

2019 ◽

Vol 39 (6) ◽

pp. 689-694

Author(s):

Joseph S Stout ◽

Carla L Granda ◽

Molly L Mancuso

Keyword(s):

Food Pellet ◽

Inhibitory Effect ◽

Dopaminergic Drugs ◽

Behavioral Studies ◽

Seeking Behavior ◽

Food Seeking ◽

And Behavior ◽

Rats And Mice ◽

Reduced Activity ◽

Over Time

Abstract Although behavioral studies of whole animals are usually undertaken on rats and mice, studies in crustaceans offer an alternative group that provides new evolutionary insights into the relationship between physiology and behavior. In the cherry shrimp Neocaridina davidi (Bouvier, 1904), food-seeking movement increases in response to glutamate (MSG), decreases when exposed to dopamine, and increases when exposed to glucose. Activity of shrimp individuals was observed in 4l tanks over twenty minutes after individuals were exposed to treatments applied directly into the water. Glutamate-stimulated seeking behavior was statistically similar to seeking behavior after exposure to food pellet filtrate. Glucose also stimulated seeking behavior, but with a reduction over time, whereas MSG-stimulated seeking behavior increased over time. Insulin reduced activity but showed no effect when paired with glucose, whereas dopamine increased activity when paired with glucose. This was contrary to the reduced activity observed when dopamine was paired with MSG. The decrease in activity after exposure to dopamine also contrasts with vertebrate (rat) models where dopaminergic drugs such as caffeine and cocaine are stimulants. The stimulatory effect of dopamine paired with glucose was unexpected given its inhibitory effect on its own or when paired with MSG. This crustacean-based model aims to give new insights regarding the role of inhibitory and stimulatory neurotransmitters on the behavior of whole crustacean individuals. These mechanisms show different results than predicted by vertebrate models, implying either differences in underlying physiology, problems with the vertebrate models, or both.

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A ventrolateral medulla-midline thalamic circuit for hypoglycemic feeding

Nature Communications ◽

10.1038/s41467-020-19980-7 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

B. Sofia Beas ◽

Xinglong Gu ◽

Yan Leng ◽

Omar Koita ◽

Shakira Rodriguez-Gonzalez ◽

...

Keyword(s):

Ventrolateral Medulla ◽

Cellular Mechanisms ◽

Posterior Portion ◽

Functional Connections ◽

Midline Thalamus ◽

Anatomical Imaging ◽

Seeking Behavior ◽

Catecholamine Neurons ◽

Food Seeking

AbstractMarked deficits in glucose availability, or glucoprivation, elicit organism-wide counter-regulatory responses whose purpose is to restore glucose homeostasis. However, while catecholamine neurons of the ventrolateral medulla (VLMCA) are thought to orchestrate these responses, the circuit and cellular mechanisms underlying specific counter-regulatory responses are largely unknown. Here, we combined anatomical, imaging, optogenetic and behavioral approaches to interrogate the circuit mechanisms by which VLMCA neurons orchestrate glucoprivation-induced food seeking behavior. Using these approaches, we found that VLMCA neurons form functional connections with nucleus accumbens (NAc)-projecting neurons of the posterior portion of the paraventricular nucleus of the thalamus (pPVT). Importantly, optogenetic manipulations revealed that while activation of VLMCA projections to the pPVT was sufficient to elicit robust feeding behavior in well fed mice, inhibition of VLMCA–pPVT communication significantly impaired glucoprivation-induced feeding while leaving other major counterregulatory responses intact. Collectively our findings identify the VLMCA–pPVT–NAc pathway as a previously-neglected node selectively controlling glucoprivation-induced food seeking. Moreover, by identifying the ventrolateral medulla as a direct source of metabolic information to the midline thalamus, our results support a growing body of literature on the role of the PVT in homeostatic regulation.

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The Anxiogenic Drug Yohimbine Reinstates Palatable Food Seeking in a Rat Relapse Model: a Role of CRF1 Receptors

Neuropsychopharmacology ◽

10.1038/sj.npp.1300964 ◽

2005 ◽

Vol 31 (10) ◽

pp. 2188-2196 ◽

Cited By ~ 102

Author(s):

Udi E Ghitza ◽

Sarah M Gray ◽

David H Epstein ◽

Kenner C Rice ◽

Yavin Shaham

Keyword(s):

Palatable Food ◽

Food Seeking

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The role of different subregions of the basolateral amygdala in cue-induced reinstatement and extinction of food-seeking behavior

Neuroscience ◽

10.1016/j.neuroscience.2007.03.025 ◽

2007 ◽

Vol 146 (4) ◽

pp. 1484-1494 ◽

Cited By ~ 43

Author(s):

R.J. McLaughlin ◽

S.B. Floresco

Keyword(s):

Basolateral Amygdala ◽

Seeking Behavior ◽

Food Seeking

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NTS and VTA oxytocin reduces food motivation and food seeking

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00201.2020 ◽

2020 ◽

Vol 319 (6) ◽

pp. R673-R683 ◽

Cited By ~ 1

Author(s):

Hallie S. Wald ◽

Ananya Chandra ◽

Anita Kalluri ◽

Zhi Yi Ong ◽

Matthew R. Hayes ◽

...

Keyword(s):

Food Intake ◽

Nucleus Tractus Solitarius ◽

Progressive Ratio ◽

Food Motivation ◽

Inhibitory Effects ◽

Self Administration ◽

Seeking Behavior ◽

Operant Reinforcement ◽

Food Seeking

Oxytocin (OT) is a neuropeptide whose central receptor-mediated actions include reducing food intake. One mechanism of its behavioral action is the amplification of the feeding inhibitory effects of gastrointestinal (GI) satiation signals processed by hindbrain neurons. OT treatment also reduces carbohydrate intake in humans and rodents, and correspondingly, deficits in central OT receptor (OT-R) signaling increase sucrose self-administration. This suggests that additional processes contribute to central OT effects on feeding. This study investigated the hypothesis that central OT reduces food intake by decreasing food seeking and food motivation. As central OT-Rs are expressed widely, a related focus was to assess the role of one or more OT-R-expressing nuclei in food motivation and food-seeking behavior. OT was delivered to the lateral ventricle (LV), nucleus tractus solitarius (NTS), or ventral tegmental area (VTA), and a progressive ratio (PR) schedule of operant reinforcement and an operant reinstatement paradigm were used to measure motivated feeding behavior and food-seeking behavior, respectively. OT delivered to the LV, NTS, or VTA reduced 1) motivation to work for food and 2) reinstatement of food-seeking behavior. Results provide a novel and additional interpretation for central OT-driven food intake inhibition to include the reduction of food motivation and food seeking.

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An insula-central amygdala circuit for behavioral inhibition

10.1101/156216 ◽

2017 ◽

Cited By ~ 1

Author(s):

Hillary Schiff ◽

Anna Lien Bouhuis ◽

Kai Yu ◽

Mario A. Penzo ◽

Haohong Li ◽

...

Keyword(s):

Behavioral Inhibition ◽

Neurotransmitter Release ◽

Neural Circuit ◽

Insular Cortex ◽

Central Amygdala ◽

Seeking Behavior ◽

Lick Suppression ◽

Food Seeking ◽

Avoidance Responses

AbstractPredicting which substances are suitable for consumption during foraging is critical for animals to survive. While food-seeking behavior is extensively studied, the neural circuit mechanisms underlying avoidance of potentially poisonous substances remain poorly understood. Here we examined the role of the insular cortex (IC) to central amygdala (CeA) circuit in the establishment of such avoidance behavior. Using anatomic tracing approaches combined with optogenetics-assisted circuit mapping, we found that the gustatory region of the IC sends direct excitatory projections to the lateral division of the CeA (CeL), making monosynaptic excitatory connections with distinct populations of CeL neurons. Specific inhibition of neurotransmitter release from the CeL-projecting IC neurons prevented mice from acquiring the “no-go” response, while leaving the “go” response largely unaffected in a tastant (sucrose/quinine)-reinforced “go/no-go” task. Furthermore, selective activation of the IC-CeL pathway with optogenetics drove unconditioned lick suppression in thirsty animals, induced aversive responses, and was sufficient to instruct conditioned action suppression in response to a cue predicting the optogenetic activation. These results indicate that activity in the IC-CeL circuit is necessary for establishing anticipatory avoidance responses to an aversive tastant, and is also sufficient to drive learning of such anticipatory avoidance. This function of the IC-CeL circuit is likely important for guiding avoidance of substances with unpleasant tastes during foraging in order to minimize the chance of being poisoned.Significance StatementThe ability to predict which substances are suitable for consumption is critical for survival. Here we found that activity in the insular cortex (IC) to central amygdala (CeA) circuit is necessary for establishing avoidance responses to an unpleasant tastant, and is also sufficient to drive learning of such avoidance responses. These results suggest that the IC-CeA circuit is critical for behavioral inhibition in anticipation of potentially poisonous substances during foraging.

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Review of Long-Term Consequences of Maternal Methamphetamine Exposure

Physiological Research ◽

10.33549/physiolres.934360 ◽

2019 ◽

pp. S219-S231 ◽

Cited By ~ 2

Author(s):

R. ŠLAMBEROVÁ

Keyword(s):

Mechanism Of Action ◽

The United States ◽

Eastern Bloc ◽

Drug Addicts ◽

Long Term Effects ◽

The Czech Republic ◽

Seeking Behavior ◽

Hard Drugs

Methamphetamine is one of the most abused hard drugs in the Czech Republic. Its popularity is high not only in Eastern Bloc of Europe but is growing in other countries around the world, including the United States. In addition, methamphetamine abuse increases in drug addicts during pregnancy. Although research into the long-term effects of prenatal methamphetamine exposure has been ongoing for many years, the exact mechanism of action and factors that may influence the effect of this drug are still not fully understood. There have been many studies that investigated the effects of addictive substances on the behavior and cognitive function of individuals during adolescence. Some studies have shown prenatal or perinatal influences, e.g. drugs, stress, hypoxia, and malnutrition, can affect drug sensitivity or drug-seeking behavior in adulthood. However, when these factors are most impactful, i.e. prenatal vs. perinatal, and which stages of the prenatal and perinatal periods are the most sensitive to these factors is not yet clear. Our laboratory specializes in research on the effects of drugs (especially methamphetamine) on rat mothers and their offspring during postnatal development, adolescence, and adulthood. This review summarizes our past results on the long-term effects of methamphetamine on the mother and her offspring, its mechanism of action, the role of maternal care, the possible emergence of long-term sensitization, and the critical neurodevelopmental periods for methamphetamine exposure.

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