Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence. Pancreatic Tumor Study Group

The enzymatic activity of protein kinase C (PKC) was measured in the cytosol and particulate fraction of parabrachial nucleus, the presumed site of conditioned taste aversion (CTA) engrams. At various time intervals after acquisition of the task (pairing saccharin consumption with subsequent LiCl poisoning) the nucleus was dissected from the frozen coronal sections. An increase (+40%) in the cytosol PKC activity was found 48 h after that pairing in comparison with controls (saline injection instead of LiCl). Particulate enzyme activity virtual did not change (-5%). Thus the total PKC activity increased significantly (21%). Qualitatively similar but less markedly expressed PKC shifts (+18% in cytosol) ere found 24 h following CTA. Twelve hours and 5 days after CTA acquisition the activity and distribution of PKC was similar to that seen in normal rats. The control experiments revealed that 6 h after LiCl injection alone (without previous saccharin consumption) translocation of PKC from the cytosol to the membrane fraction (found previously 1 h after LiCl injection alone) still persisted but did not differ from that found 6 h after its pairing with saccharin drinking (CTA). It is concluded that acquisition of conditioned taste aversion may be followed by synthesis of PKC rather than by its translocation or downregulation.     

Role of the perirhinal cortex in rats' conditioned taste aversion response memorization.

The role of the perirhinal cortex (PC) in conditioned taste aversion (CTA) learning was investigated in Long-Evans rats. CTA was induced by the intraperitoneal administration of LiCl 60 min after saccharin-sweetened water drinking. The PC was reversibly inactivated by the stereotaxic administration of tetrodotoxin (TTX) 60 min before saccharin drinking, immediately after saccharin drinking (Experiment 1), 6 or 24 hr after LiCl administration (Experiment 2), and 60 min before CTA retrieval testing (Experiment 3). Only pre-saccharin drinking PC inactivation disrupted CTA. Thus, PC integrity is necessary only during the earliest phases of CTA mnemonic processing, that is, taste information acquisition and early gustatory memory elaboration. The results are discussed in relation to PC connectivity and PC temporal involvement in the memorization process of other aversive responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hypothermia on the acquisition of conditioned taste aversion in rats.

Analyzed the mechanism of conditioned taste aversion (CTA) by subjecting 131 male and hooded rats in 5 experiments to reduced body temperature during various phases of CTA acquisition. A 15-min access to .1% saccharin served as the CS, and an ip injection of LiCl (.15 M, 4% of body weight) given 30 min later served as the UCS. Hypothermia (cooling to 20-22°C colonic temperature) alone or combined with anesthesia (Nembutal 20 or 40 mg/kg) did not prevent CTA acquisition when applied during the CS-UCS interval. Hypothermia induced immediately after LiCl administration to anesthetized or unanesthetized Ss failed to disrupt CTA or to increase neophobic rejection of saccharin. On the other hand, hypothermic Ss were not able to form the short-term gustatory trace when the CS (2% saccharin, 1% of body weight) was injected ip, although this procedure yielded significant CTA in euthermic Ss. It is concluded that the most vulnerable link of CTA acquisition is the formation of the short-term gustatory trace. Persistence of the short-term trace, its association with poisoning, and consolidation of the permanent CTA engram are accomplished by mechanisms that are resistant to hypothermia and/or anesthesia. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned taste aversion is disrupted by prolonged retrograde effects of intracerebral injection of tetrodotoxin in rats.

Acquisition of conditioned taste aversion (CTA) is disrupted when 10 ng tetrodotoxin (TTX) is injected into both parabrachial nuclei of rats immediately after saccharin drinking and before LiCl poisoning (S. F. Ivanova & J. Bure?, in press). Further analysis of this finding showed that parabrachial TTX injection (1) elicited retrograde amnesia also when applied 1, 2, or 4 days but not 8 days after CTA acquisition; (2) did not abolish CTA produced by 2 or 3 saccharin–LiCl pairings; (3) did not cause persistent increase of quinine threshold; and (4) elicited anterograde CTA amnesia when applied 1 but not 2, 4, or 8 days before CTA acquisition. TTX-induced amnesia is not due to persistent gustatory agnosia but rather to disruption of the protracted consolidation of the permanent CTA engram by prolonged cessation of impulse activity in the information storing network. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alcohol-induced conditioned taste aversions in chemically labyrinthectomized rats

Male rats were chemically labyrinthectomized (n = 22) by intratympanic injections of sodium arsanilate, and control rats (n = 15) received intratympanic injections of isotonic saline. All rats were tested for labyrinthine integrity and then adjusted to a 23 h.d-1 water deprivation schedule. Both labyrinthectomized and control rats were exposed to a conditioned taste aversion (CTA) procedure or a control procedure. The CTA technique involved pairing a novel saccharin taste with subsequent intraperitoneal injection of ethanol (1.5 g.kg-1; 15% solution). The control CTA procedure paired a novel saccharin taste with injections of isotonic saline. Following two conditioning trials and 3 d of water only, saccharin preference ratios were obtained in two-bottle choice tests (saccharin vs. water) over 4 consecutive days. Control rats conditioned with ethanol exhibited a strong CTA (p < 0.01) relative to control rats injected with saline. Labyrinthectomized rats drinking saccharin followed by ethanol injections showed a strong CTA (p < 0.01) if conditioning occurred 29-30 d post-labyrinthectomy. However, CTA's were not apparent in labyrinthectomized rats conditioned with ethanol 19 d post-labyrinthectomy. Thus, ethanol-induced CTA formation varied across the post-labyrinthectomy time period.     

Taste aversion learning in fyn mutant mice.

Conditioned taste aversion (CTA) learning is a robust form of classical conditioning in which animals rapidly associate a flavor with aversive internal symptoms. The present study assessed CTA learning in transgenic mice deficient in a specific nonreceptor tyrosine kinase (the fyn mutant). Fyn mutants show impaired long-term potentiation and marked deficits in acquisition of spatial learning tasks. To assess whether they are also impaired in CTA learning. fyn mutant and wild-type mice received 2 conditioning trials consisting of access to a flavored solution followed by administration of LiCl. Fyn mutant mice acquired significant CTAs following a single conditioning trial and these aversions were comparable to those seen in wild-type mice. These results indicate that the fyn mutation does not interfere with the acquisition of CTAs and hence that this mutation is not associated with a global learning deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attenuation of ethanol-induced conditioned taste aversion in mice sensitized to the locomotor stimulant effects of ethanol.

This study examined the effect of repeated ethanol (EtOH) injections that induced behavioral sensitization on subsequent acquisition of EtOH- and lithium chloride (LiCl)-induced conditioned taste aversion (CTA). CTA acquisition was assessed in independent groups of EtOH-sensitized and nonsensitized genetically heterogeneous female mice after injections of saline; 1, 2, or 4 g/kg EtOH; or 2 or 4 mEq/kg LiCl. Saline and 1 g/kg EtOH did not induce CTA. Four g/kg EtOH and 4 mEq/kg LiCl induced similar levels of CTA in EtOH-sensitized and nonsensitized groups. CTA induced by 2 g/kg EtOH and 2 mEq/kg LiCl was attenuated in EtOH-sensitized mice compared with nonsensitized counterparts. Thus, a sensitizing regimen of EtOH preexposure resulted in both a decrease in EtOH and LiCl aversion and an increase in EtOH locomotor sensitivity; such changes could ultimately contribute to enhanced EtOH intake and potentially to EtOH abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned taste aversion in lean and obese rats with ventromedial hypothalamic knife cuts.

Assessed the development of a conditioned taste aversion (CTA) in 60 female Sprague-Dawley rats made hyperphagic with parasagittal knife cuts in the ventromedial hypothalamus (VMH). Ss were water deprived and presented with a .1% saccharin solution paired with injections of either LiCl or NaCl. In Exp I, VMH Ss tested at a nonobese weight level did not differ from sham-operated controls in acquisition and extinction of the CTA. In Exp II, moderately obese VMH Ss displayed a stronger CTA than did sham-operated controls as evidenced by slower extinction. A 2nd group of obese VMH Ss given an amount of LiCl equivalent to that given to the controls also displayed retarded extinction of the CTA. Results reflect an obesity-induced suppression in appetitive motivation. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Re-examination of amphetamine-induced conditioned suppression of tastant intake in rats: The task-dependent drug effects hypothesis.

This study reexamined Grigson's reward comparison hypothesis (1997), which claimed to have resolved the paradox of addictive, rewarding drugs manifesting an aversive effect in the conditioned taste aversion (CTA) paradigm. Here, the authors compared the conditioned suppression effects of lithium chloride (LiCl) and amphetamine in a series of three experiments. In Experiment 1, the concentrations of saccharin solution (conditioned stimulus [CS]) and the doses of amphetamine or LiCl (unconditioned stimulus [US]) were manipulated. In Experiment 2, the effects of employing backward versus forward pairings of the CS and US were compared. Finally, in Experiment 3, the additivity of amphetamine's reward property and LiCl's aversive property was examined. The results of these experiments, respectively, indicated that: (1) manipulating saccharin solution concentrations does not distinguish the suppression effect caused by rewarding or aversive effects when amphetamine or LiCl served as the US; (2) both backward and forward pairings produced suppression of saccharin solution intake regardless of whether amphetamine or LiCl was used as the US; and (3) combining amphetamine and LiCl did not diminish the suppression effect, as would be expected if they had opposing mechanisms for the effects; instead, an additive effect occurred. Taken together, these results suggest that the drug of abuse amphetamine and the emetic drug LiCl both possess aversive properties in the CTA paradigm. No rewarding effects of amphetamine were detected in our experimental data. In all, our results do not support the Grigson's reward comparison hypothesis (1997) and a new "task-dependent drug effects hypothesis" is proposed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Forebrain structures specifically activated by conditioned taste aversion.

This study investigates which forebrain structures show Fos protein expression during conditioned taste aversion (CTA) acquisition and whether Fos expression depends on the aversion strength. A novel taste paired with an intraperitoneal injection of a low dose of the malaise-inducing agent lithium chloride (LiCl) induced a weak CTA, whereas associating this novel taste with a high dose of LiCl induced a strong CTA. Increasing the strength of the gastric malaise alone enhanced Fos expression in central, basal, and lateral amygdala nuclei and decreased Fos expression in the nucleus accumbens core. Taste-malaise association induced specific Fos activation in the insular cortex (with both the low and the high doses of LiCl) and the nucleus accumbens shell (with the high LiCl dose only). No significant variation of Fos expression was measured in the perirhinal cortex. Several forebrain areas may be sites of taste-malaise convergence during CTA acquisition depending on the strength of the aversion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetic Correlational Analyses of Ethanol Reward and Aversion Phenotypes in Short-Term Selected Mouse Lines Bred for Ethanol Drinking or Ethanol-Induced Conditioned Taste Aversion.

Short-term selective breeding created mouse lines divergent for ethanol drinking (high drinking short-term selected line [STDRHI], low drinking [STDRLO]) or ethanol-induced conditioned taste aversion (CTA; high [HTA], low [LTA]). Compared with STDRLO, STDRHI mice consumed more saccharin and less quinine, exhibited greater ethanol-induced conditioned place preference (CPP), and showed reduced ethanol stimulation and sensitization under some conditions; a line difference in ethanol-induced CTA was not consistently found. Compared with LTA, HTA mice consumed less ethanol but were similar in saccharin consumption, sensitivity to ethanol-induced CPP, and ethanol-induced locomotor stimulation and sensitization. These data suggest that ethanol drinking is genetically associated with several reward-and aversion-related traits. The interpretation of ethanol-induced CTA as more genetically distinct must be tempered by the inability to test the CTA lines beyond Selection Generation 2. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic morphine treatment exaggerates the suppressive effects of sucrose and cocaine, but not lithium chloride, on saccharin intake in Sprague-Dawley rats.

Three experiments examined the effect of chronic morphine treatment on cocaine-, sucrose-, and lithium chloride (LiCl)-induced suppression of saccharin intake in Sprague-Dawley rats. All rats were either water- or food-deprived and then implanted subcutaneously with 1 morphine (75 mg) or vehicle pellet for 5 days. They were then given brief access to 0.15% saccharin and soon thereafter injected with either cocaine (10 mg/kg sc) LiCl (0.009 M, 1.33 ml/100 g body weight ip), or saline, or in Exp 2, given a 2nd access period to either a preferred 1.0 M sucrose solution ot the same 0.15% saccharin solution. There was 1 taste–drug or taste–taste paring per day for a number of days. The results showed that a history of chronic morphine treatment exaggerated the suppressive effects of a rewarding sucrose solution and cocaine but not those of the aversive agent, LiCl. These data provide further support for the reward compairison hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Column-switching high-performance liquid chromatographic assay for determination of apigenin and acacetin in human urine with ultraviolet absorbance detection

Postweaning social isolation can influence the sensitivity of rats to several effects of drugs of abuse. The present study investigated the influence of postweaning housing conditions on the sensitivity of rats to the aversive effects of a number of psychoactive agents using a conditioned taste aversion (CTA) test procedure. Development of a CTA was assessed by pairing administration of the drug with the consumption of a 0.05% (weight/volume) saccharin solution in water-deprived (18 h) rats in a 20 min drinking period. Saccharin consumption was then measured in 20 min test sessions over the next 4 consecutive days. Consumption of saccharin solution was significantly reduced in both isolated and enriched rats following administration of d-amphetamine (2 mg/kg), cocaine (30 mg/kg), morphine (10 mg/kg), nicotine (1.0 mg/kg), caffeine (20 mg/kg), alcohol (1.5 g/kg), and LiCl (0.15 M, 4 ml/kg). There was no significant effect of housing conditions on the CTA induced by cocaine, nicotine, alcohol, or LiCl; however, isolation-reared rats were found to be less sensitive to the aversive effects of d-amphetamine, morphine, and caffeine in this paradigm. These results suggest that rearing rats in social isolation induces an attenuation in sensitivity to the aversive effects of some psychoactive agents.     

Conditioned responses to a taste conditioned stimulus paired with lithium chloride administration.

The present experiments examined whether behavioral conditioned responses (CRs) develop to lithium chloride (LiCl)-paired tastes and whether these CRs are similar to the behaviors that follow administration of the drug. Rats were exposed to a saccharin solution via intraoral infusions before being injected with either LiCl or saline. CRs were assessed after conditioning when the saccharin conditioned stimulus (CS) was delivered alone. The unconditioned response (UCR) to LiCl delivery is a very distinctive posture that has been termed "lying-on-belly." The present study indicates that this behavior pattern also occurs after the delivery of a LiCl-paired taste solution. The similarity between these unconditioned and conditioned behaviors is consistent with the hypothesis that responses are conditioned during taste aversion acquisition and that CRs are similar to those that are generated by the drugs used in conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disruption of saccharin-aversion learning in rats by cortical spreading depression in the CS-US interval.

Taught 80 rats to associate the flavor of saccharin (.1%) with the sickness produced by ip injection of 100 mg/kg of lithium chloride (LiCl) 5 hr. after drinking. A choice test on the next day revealed 90% saccharin preference in naive Ss and 80% water preference in the training group. Bilateral cortical spreading depression (CSD) interfered with the aversion most clearly when applied 3 hr. after saccharin ingestion. Less complete aversion was induced when CSD was elicited 5 min. after saccharin administration or 15 min. before LiCl injection. The CSD evoked 5 min. after LiCl injection was without any amnesic effect. It is suggested that the cortical gustatory trace prolongs the temporal storage of taste cues at the bulbar level and helps to bridge the long CS-UCS delays typical for gustatory-visceral learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mouse model of fragile X syndrome: Behavioral and hormonal response to stressors.

Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice’s increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiation of odor by taste in rats: Tests of some nonassociative factors.

Three experiments with 94 male Sprague-Dawley rats tested the contribution of nonassociative neophobia and sensitization to the potentiation of odor by taste. In Exp I, neophobia for almond odor (O), saccharin taste (T), and odor-taste compound (OT) cues was tested before and after noncontingent LiCl poisoning and compared with conditioned aversions produced by OT–LiCl temporal pairing. The OT compound potentiated unconditioned neophobia, but there was no evidence of poison-enhanced neophobia, disinhibition of neophobia, or sensitization by noncontingent LiCl; temporal pairing produced aversions for the compound and its elements. In Exp II, generalization to a novel odor was tested after O–LiCl or compound OT–LiCl pairing. The potentiated odor aversion did not generalize to the novel odor; it was specific to the odor paired with taste and LiCl. In Exp III, potentiation of the odor component by a discriminant or nondiscriminant taste component was tested. Potentiation was evident only when a novel discriminant taste was in compound with odor prior to LiCl poisoning. Results from all experiments support an associative "indexing" hypothesis of the potentiation effect in rats. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parabrachial gustatory lesions impair taste aversion learning in rats.

Lesions in the gustatory zone of the parabrachial nuclei (PBN) severely impair acquisition of a conditioned taste aversion (CTA) in rats. To test whether this deficit has a memorial basis, 15 intact rats and 10 rats with PBN lesions (PBNX) received 7 intraoral taste stimulus infusions (30 sec, 0.5 ml) distributed over a 30.5-min period after either LiCl or NaCl injection. This task measures the rapid formation of a CTA and has minimum demands on memory. LiCl-injected intact rats progressively changed their oromotor response profiles from one of ingestion to one of aversion. NaCl-injected intact rats did not change their ingestive pattern of responding. In contrast, there was no difference between LiCl- and NaCl-injected PBNX rats. These same PBNX rats failed to avoid licking the taste stimulus when tested in a different paradigm. A simple impairment in a memorial process is not likely the basis for the CTA deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disruption of conditioned taste aversion in the rat by stimulation of amygdala: A conditioning effect, not amnesia.

Conducted 2 experiments with a total of 143 male Wistar rats to determine whether the disruption of conditioned taste aversion by amygdaloid brain stimulation (BST) during conditioning could be attributed to the stimulus properties of the BST. In Exp I, Ss receiving BST (a) while drinking saccharin, (b) during the onset of LiCl toxicosis, or (c) in the interval between taste exposure and toxicosis drank significantly more saccharin solution during a 48-hr retest than implanted or unoperated controls receiving similar taste–toxicosis pairings. In contrast, Ss receiving BST during both conditioning and retention trials developed a strong conditioned aversion. Exp II confirmed that BST formed a compound with the taste of the saccharin solution. A small but significant aversion was displayed by groups exposed to BST plus taste during conditioning and to either taste alone or BST alone during the retest. Again, the group presented with BST and taste prior to and following LiCl toxicosis displayed a strong conditioned aversion. Results suggest that disruption of conditioned taste aversion with amygdaloid BST represents a conditioning effect, not amnesia. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Propensity to form conditioned taste aversions augments anorexia in obese (Ob/Ob) mice with B16 melanoma.

Obese mice (OB) with B16 melanoma become anorectic, but lean mice (LN) do not. Present studies suggest that this difference reflects a greater bent for OB to form conditioned taste aversions (CTAs). In Exp 1, healthy OB formed stronger CTAs than LN to a saccharin taste paired with lithium chloride (LiCl; 3 mEq/kp intraperitoneally [ip]). In Exp 2, the OB–LN difference of Exp 1 was decreased by giving naltrexone (10 mg/kg subcutaneously [sc]) before LiCl, which suggested opiate involvement. Exp 3 showed that OB tumor anorexia vanishes if foods dissociated from tumor growth are given: OB fed a constant diet became anorectic 16 days after B16 inoculation; giving a new diet on Day 16 delayed anorexia onset for 8 days; a 2nd new diet on Day 32 abolished anorexia for 24 hrs. LN with tumors ate all diets at nontumor control levels. OB survived melanoma longer than LN regardless of diet, but OB fed a varied diet died first; thus, anorexia may enhance OB survival. (PsycINFO Database Record (c) 2010 APA, all rights reserved)