lithium-chloride and Pain

Pairing a taste with either internal pain or nausea, despite equivalent effects on voluntary consumption, has dissociable effects on hedonic responses: Only pairing with nausea results in the production of disgust reactions, while pairing with internal pain results in conditioned fear as indicated by immobility. Here, we use orofacial reactions to examine the hedonic responses elicited by contextual, nonflavor, cues paired with nausea produced by injection of lithium chloride (LiCl) or internal pain caused by injection of hypertonic saline. In Experiment 1, aversive orofacial responses were the specific context-elicited behaviors in the rats injected with LiCl, whereas immobility was seen in the animals injected with hypertonic saline. In Experiment 2, rats first received discriminative training with two contexts, where one context was paired with LiCl or hypertonic saline, and the other context with isotonic saline. After this, rats were intraorally infused with a flavor (conditioned stimulus (CS) +) in the paired context, and with a different flavor (CS-) in the unpaired context. Second-order conditioning was then examined in a test conducted in the unpaired context. The infusion of the CS + flavor produced aversive orofacial responses in the rats injected with LiCl but immobility in the subjects injected with hypertonic saline. The results suggest that nonflavor cues support conditioned hedonic responses in the same way as flavor cues, which implies that the quality of aversion learning (conditioned nausea vs. fear) is primarily determined by the nature of the aversive event and not the type of conditioned cue. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Topics: Affect; Animals; Avoidance Learning; Behavior, Animal; Conditioning, Classical; Cues; Lithium Chloride; Male; Nausea; Pain; Rats, Wistar; Taste

Pairing a taste with either internal pain (e.g., from hypertonic saline injection) or nausea (e.g., from LiCl administration) will reduce subsequent consumption of that taste. Here we examine the responses to a taste paired with either hypertonic saline or LiCl using the analysis of licking microstructure (mean lick cluster size: Experiments 1-3), taste reactivity (examining the distribution of appetitive and aversive orofacial responses: Experiments 2-3), and immobility (as a measure of fear: Experiments 2-3). At both high (10 ml/kg 0.15 M LiCl, 10 ml/kg 1.5 M NaCl) and low dose levels (2 ml/kg 0.15 M LiCl, 4 ml/kg 1.5 M NaCl), pairing a taste with either LiCl-induced nausea or internal pain produced by hypertonic NaCl caused reductions in voluntary consumption, in appetitive taste reactivity responses, and in lick cluster size. However, only pairing with LiCl resulted in conditioned aversive taste reactivity responses to the taste. In contrast, pairing with hypertonic NaCl resulted in the taste eliciting higher levels of immobility (reflecting fear) than did pairing the taste with LiCl. The clearly dissociable effects of LiCl and hypertonic saline on aversive taste reactivity and fear responses, despite equivalent effects on consumption, demonstrates selective conditioning effects between internal pain and nausea. (PsycINFO Database Record

Topics: Analysis of Variance; Animals; Appetite; Avoidance Learning; Conditioning, Classical; Dose-Response Relationship, Drug; Drinking Behavior; Fear; Lithium Chloride; Male; Nausea; Pain; Rats; Rats, Wistar; Saline Solution, Hypertonic; Taste; Water Deprivation

The GABAergic tail of the ventral tegmental area (tVTA), also named rostromedial tegmental nucleus (RMTg), exerts an inhibitory control on dopamine neurons of the VTA and substantia nigra. The tVTA has been implicated in avoidance behaviors, response to drugs of abuse, reward prediction error, and motor functions. Stimulation of the lateral habenula (LHb) inputs to the tVTA, or of the tVTA itself, induces avoidance behaviors, which suggests a role of the tVTA in processing aversive information. Our aim was to test the impact of aversive stimuli on the molecular recruitment of the tVTA, and the behavioral consequences of tVTA lesions. In rats, we assessed Fos response to lithium chloride (LiCl), β-carboline, naloxone, lipopolysaccharide (LPS), inflammatory pain, neuropathic pain, foot-shock, restraint stress, forced swimming, predator odor, and opiate withdrawal. We also determined the effect of tVTA bilateral ablation on physical signs of opiate withdrawal, and on LPS- and LiCl-induced conditioned taste aversion (CTA). Naloxone-precipitated opiate withdrawal induced Fos in μ-opioid receptor-positive (15%) and -negative (85%) tVTA cells, suggesting the presence of both direct and indirect mechanisms in tVTA recruitment during withdrawal. However, tVTA lesion did not impact physical signs of opiate withdrawal. Fos induction was also present with repeated, but not single, foot-shock delivery. However, such induction was mostly absent with other aversive stimuli. Moreover, tVTA ablation had no impact on CTA. Although stimulation of the tVTA favors avoidance behaviors, present findings suggest that this structure may be important to the response to some, but not all, aversive stimuli.

Topics: Animals; Antimanic Agents; Behavior, Animal; Carbolines; Conditioning, Classical; Disease Models, Animal; Lipopolysaccharides; Lithium Chloride; Male; Morphine Dependence; Naloxone; Narcotic Antagonists; Neuralgia; Neurotoxins; Olfactory Perception; Pain; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Substance Withdrawal Syndrome; Ventral Tegmental Area

Animals made ill by intraperitoneal injection with toxins, such as lithium chloride (LiCl) or lipopolysaccharides (LPS), or presented with cues associated with LiCl become hyperalgesic [Pain 56 (1994) 227]. The descending pronociceptive neurocircuitry and spinal pharmacology that underlie these effects bear the same features as those that mediate analgesic tolerance to morphine [Neurosci. Biobehav. Rev. 23 (1999) 1059]. Thus, we examined whether LiCl, LPS or cues paired with LiCl could reduce morphine analgesia. Morphine analgesia in the tail flick test was reduced 24 h but not 7 days following injection with LiCl, and 24 h following injection with LPS. In addition, morphine analgesia was reduced in the hot plate test 40 min and 24 h following LiCl. Furthermore, these effects occurred in the absence of detectable hyperalgesia indicating that illness-induced tolerance was not the result of an increase in pain sensitivity offsetting analgesia. Finally, rats tested in a context associated with LiCl demonstrated less morphine analgesia than rats tested in a context not associated with LiCl or rats naive to LiCl suggesting that illness activates descending mechanisms that antagonize analgesia rather than simply desensitizing opioid receptors. Thus, in addition to provoking hyperalgesia, illness-inducing agents also activate endogenous antianalgesic mechanisms.

Topics: Acute Disease; Analgesia; Analgesics, Opioid; Animals; Conditioning, Psychological; Cues; Disease; Hyperalgesia; Lipopolysaccharides; Lithium Chloride; Male; Morphine; Neuroimmunomodulation; Pain; Pain Measurement; Pain Threshold; Rats; Rats, Wistar

Recent research indicates that the sensitization that results from repeated drug or non-drug stress exposure may develop into a pattern of alternating increases and decreases (i.e., oscillation) in response to each subsequent stressor exposure. Oscillation, with or without prior sensitization, has been observed for a number of drug and non-drug stressors, and for various neurochemical and endocrine endpoints. The present studies investigated whether oscillation also occurs in the behavioral and endocrine effects of repeated morphine treatment and if a drug that normalizes the mood swings of bipolar disorder in humans will also attenuate drug oscillation in this animal model. In the first experiment, rats were given 1-5 pretreatments with morphine (15 mg/kg, i.p.), separated by 1-week intervals with the last injection occurring 1 hour prior to being tested for stressor-induced (i.e., 5 seconds, 2-mA electric footshock) hypoalgesia, as measured by latency to paw-lift or jump from a hot-plate. Plasma beta-endorphin also was measured. The second experiment replicated the behavioral findings of the first study and, in addition, assessed the effect of continuous lithium chloride, in the drinking water, on morphine-induced oscillation. Caffeine was used as a partial control for the lithium. The results were that one injection of morphine enhanced stress-induced hypoalgesia and subsequent morphine administrations resulted in oscillation. Beta-endorphin exhibited sensitization but not oscillation, suggesting that it did not mediate oscillation of the behavioral response. In addition, lithium, but not caffeine, eliminated oscillations of the behavioral response without affecting its initial enhancement.

Topics: Analysis of Variance; Animals; beta-Endorphin; Caffeine; Electroshock; Lithium Chloride; Male; Morphine; Oscillometry; Pain; Rats; Rats, Sprague-Dawley

Rats were used to determine whether stress-induced analgesia (SIA) can be produced by conditioning with interoceptive stimuli (LiCl) as with exteroceptive stimuli (footshock). SIA was measured using a tail-flick test. As expected, unavoidable footshock as well as conditioning with footshock produced SIA. In contrast, conditioning with LiCl failed to cause SIA. The findings support the notion of functional differences in neural substrates for conditioning by exteroceptive and interoceptive cue.

Topics: Animals; Avoidance Learning; Chlorides; Conditioning, Classical; Cues; Electroshock; Lithium; Lithium Chloride; Male; Pain; Rats; Rats, Inbred Strains; Sensation; Sensory Thresholds; Stress, Physiological

In rats, the conditioned place and taste aversions produced by 31.8 mg/kg lithium chloride were compared with those produced by 10 mg/kg gallamine in Experiment 1 and 20 mg/kg or 2.5 mg/kg naloxone in Experiments 2 and 3, respectively. Lithium produced stronger taste aversions than gallamine or the two doses of naloxone, but gallamine and naloxone each produced stronger place aversions than lithium. These findings support the distinction between two kinds of drug-induced aversive effects, having different associative properties. One effect, called sickness, is more associable with taste than with place cues; the second effect is, like pain, more associable with place than with taste.

Topics: Animals; Association; Avoidance Learning; Chlorides; Gallamine Triethiodide; Lithium; Lithium Chloride; Male; Naloxone; Nausea; Pain; Rats; Rats, Inbred Strains; Spatial Behavior; Taste