Learned taste aversions in rats as a function of dosage, concentration, and route of administration of LiCl

Nachman, Marvin; Ashe, John H.

doi:10.1016/0031-9384(73)90089-9

Cited by 418 publications

(219 citation statements)

References 25 publications

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“…However, responses during the first NaCl trial could include the beginnings of extinction processes. Furthermore, intake on LiCl Trial 3 was small, corresponding to a dose (0.38 mEq/kg) that likely produces only a moderate malaise and CTA (Nachman & Ashe, 1973), 2 and is consistent with the suggestion that rats learn to regulate LiCl drinking at a rate that minimizes toxicosis (CrossMellor et al, 2004). Analysis of the first LiCl acquisition trial to reveal the unconditioned effects of LiCl is also indeterminate.…”

Section: Dissociation Of Associative and Unconditioned Effects Of Licsupporting

confidence: 80%

Temporal and Qualitative Dynamics of Conditioned Taste Aversion Processing: Combined Generalization Testing and Licking Microstructure Analysis.

Baird

John

Nguyen

2005

Behavioral Neuroscience

133

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The pattern of licking microstructure during various phases of a conditioned taste aversion (CTA) was evaluated. In Experiment 1, rats ingested lithium chloride (LiCl) for 3 trials and were then offered sodium chloride (NaCl) or sucrose on 3 trials. A CTA to LiCl developed and generalized to NaCl but not to sucrose. CTA intake suppression was characterized by reductions in burst size, average ingestion rate, and intraburst lick rate, and increases in brief pauses and burst counts. Compared with previous studies, LiCl licking shifted from a pattern initially matching that for normally accepted NaCl to one matching licking for normally avoided quinine hydrochloride by the end of the 1st acquisition trial. In Experiment 2, a novel paradigm was developed to show that rats expressed CTA generalization within 9 min of their first LiCl access. These results suggest that licking microstructure analysis can be used to assay changes in hedonic evaluation caused by treatments that produce aversive states.

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Section: Dissociation Of Associative and Unconditioned Effects Of Licsupporting

confidence: 80%

Temporal and Qualitative Dynamics of Conditioned Taste Aversion Processing: Combined Generalization Testing and Licking Microstructure Analysis.

Baird

John

Nguyen

2005

Behavioral Neuroscience

133

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“…Since the mid 1950s it has been known that rats avoid intake of a gustatory conditioned stimulus (CS), such as saccharin, after it has been paired with an aversive, illness-inducing agent such as lithium chloride (LiCl) or x-radiation [9][10][11]. This phenomenon, referred to as a conditioned taste aversion (CTA), was found to occur following a single taste-illness pairing and even when using relatively long intervals between access to the CS and exposure to the aversive unconditioned stimulus (US).…”

Section: The Model: Experimenter Delivered Drugmentioning

confidence: 99%

Reward comparison: the Achilles’ heel and hope for addiction

Grigson

2008

Drug Discovery Today: Disease Models

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In the words of the late Charles Flaherty, reward comparison is commonplace. Rats and man, it appears, compare all rewards and this capacity likely contributes to our ability to select the most appropriate reward/behavior (food, water, salt, sex), at the most ideal level (e.g., a certain sweetness), at any given time. A second advantage of our predisposition for reward comparison is that the availability of rich alternative rewards can protect against our becoming addicted to any single reward/behavior. Thus, the potential protective effects of natural rewards/enrichment are addressed. Despite this, behavior can become inflexible when, through the development of addiction, stress, drug, or cues elicit craving, withdrawal, and ultimately, drug-seeking. Drug-seeking corresponds with a 'window of inopportunity', when even potent natural rewards have little or no impact on behavior. During this time, there is a unitary solution to the need state, and that solution is drug. The present animal model explores this 'window of inopportunity' when natural rewards are devalued and drug-seeking is engaged and considers a mode of possible intervention.

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“…Both LiCl and GLP-1 produce similar physiological consequences, many of which are proxies of nausea/ malaise. These effects include a reduction in food intake (McCann et al, 1989;Tang-Christensen et al, 1996) and gastric emptying (McCann et al, 1989;Wettergren et al, 1993), generation of CTA (Nachman and Ashe, 1973;Thiele et al, 1997) and pica (Mitchell et al, 1976;Kanoski et al, 2012). GLP-1 antagonists have successfully been used to block the aversive-like behaviors (eg reduction in food intake, pica, CTA) induced by LiCl (Rinaman, 1999b;Seeley et al, 2000), indicating that these manifestations of LiCl are, at least in part, mediated through GLP-1R signaling.…”

Section: Discussionmentioning

confidence: 99%

“…The unconditioned dopaminesuppressive effects of LiCl observed here may influence the learning process that occurs during the development of a conditioned taste aversion. LiCl, when paired with a novel, palatable taste, like a sucrose solution, conditions voluntary avoidance (Nachman and Ashe, 1973) or active rejection (Parker and Carvell, 1986;Spector et al, 1988) of the taste upon subsequent exposure. We have previously shown that pairing of an intra-oral sucrose solution with LiCl can condition dopamine release patterns in addition to behavior.…”

Section: Discussionmentioning

confidence: 99%

“…Illness resulting from LiCl is also known to condition taste avoidance or aversion (CTA; Nachman and Ashe, 1973;Parker and Carvell, 1986;Spector et al, 1988). Systemic LiCl activates neurons in circumventricular organs (eg area postrema) as well as a discrete population of hindbrain neurons that make and release glucagon-like peptide-1 (GLP-1) (Rinaman, 1999a;Thiele et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors

Fortin

Chartoff

Roitman

2015

Neuropsychopharmacol

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Unconditioned rewarding stimuli evoke phasic increases in dopamine concentration in the nucleus accumbens (NAc) while discrete aversive stimuli elicit pauses in dopamine neuron firing and reductions in NAc dopamine concentration. The unconditioned effects of more prolonged aversive states on dopamine release dynamics are not well understood and are investigated here using the malaise-inducing agent lithium chloride (LiCl). We used fast-scan cyclic voltammetry to measure phasic increases in NAc dopamine resulting from electrical stimulation of dopamine cell bodies in the ventral tegmental area (VTA). Systemic LiCl injection reduced electrically evoked dopamine release in the NAc of both anesthetized and awake rats. As some behavioral effects of LiCl appear to be mediated through glucagon-like peptide-1 receptor (GLP-1R) activation, we hypothesized that the suppression of phasic dopamine by LiCl is GLP-1R dependent. Indeed, peripheral pretreatment with the GLP-1R antagonist exendin-9 (Ex-9) potently attenuated the LiCl-induced suppression of dopamine. Pretreatment with Ex-9 did not, however, affect the suppression of phasic dopamine release by the kappa-opioid receptor agonist, salvinorin A, supporting a selective effect of GLP-1R stimulation in LiCl-induced dopamine suppression. By delivering Ex-9 to either the lateral or fourth ventricle, we highlight a population of central GLP-1 receptors rostral to the hindbrain that are involved in the LiClmediated suppression of NAc dopamine release. Neuropsychopharmacology (2016) 41, 906-915;

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Learned taste aversions in rats as a function of dosage, concentration, and route of administration of LiCl

Cited by 418 publications

References 25 publications

Temporal and Qualitative Dynamics of Conditioned Taste Aversion Processing: Combined Generalization Testing and Licking Microstructure Analysis.

Temporal and Qualitative Dynamics of Conditioned Taste Aversion Processing: Combined Generalization Testing and Licking Microstructure Analysis.

Reward comparison: the Achilles’ heel and hope for addiction

The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors

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