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)     

Insular cortex lesions and morphine-induced suppression of conditioned stimulus intake in the rat.

The present experiment examined the influence of insular cortex (IC) lesions on the intake of a taste stimulus in a consummatory procedure that used morphine as the unconditioned stimulus. In normal rats, morphine caused a rapid reduction in saccharin intake when the taste was novel but not when it was familiar. Irrespective of stimulus novelty, morphine had little influence on the saccharin consumption of IC-lesioned rats. The results are discussed in terms of a lesion-induced disruption of (i) a reward comparison mechanism and (ii) the perception of taste novelty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multielemental stimulus control: Effects of saccharin concentration on a discriminated morphine-saccharin taste aversion.

The effects of saccharin concentration on the stimulus control by a compound stimulus consisting of morphine, saccharin (0.01, 0.03, or 0.10%, wt/vol), and a ball bearing drinking nozzle in a discriminated taste aversion (DTA) procedure were examined in rats (Rattus norvegicus). In paired rats injections of lithium followed presentation of this compound stimulus, whereas in unpaired rats saline injections followed this stimulus. DTA acquisition was more rapid at higher saccharin concentrations. In testing with each individual stimulus element, stimulus control was clearly exerted by all 3 stimulus elements. When another stimulus element was presented jointly with saccharin, behavioral control was similar to that of saccharin alone. Behavioral control by saccharin increased with saccharin concentration. However, behavioral control by the 2 other stimulus elements was relatively unaffected when the saliency of the saccharin element was increased. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned aversion to distinct environmental stimuli resulting from gastrointestinal distress.

In Exp I, 40 male Sprague-Dawley-derived rats subjected to apomorphine-induced malaise following a 2-min placement in a black compartment avoided this black compartment significantly more than 10 controls in a choice situation. The degree of aversion, however, was substantially reduced when Ss were provided water (or saccharin) in the black compartment during conditioning and testing. Ss learned to suppress consumption of fluid in the black compartment. In Exp II, 10 Ss were made ill in the black compartment. Later, when drinking saccharin (or saline) preceded placement in the black compartment, Ss learned to suppress consumption of that fluid. The black compartment had become a conditioned reinforcer for taste aversion. (19 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gustatory insular cortex lesions disrupt drug-induced, but not lithium chloride-induced, suppression of conditioned stimulus intake.

Rats suppress intake of a normally preferred 0.15% saccharin conditioned stimulus (CS) when it is paired with an aversive agent like lithium chloride (LiCl) or a preferred substance such as sucrose or a drug of abuse. The reward comparison hypothesis suggests that rats avoid intake of a saccharin cue following pairings with a drug of abuse because the rats are anticipating the availability of the rewarding properties of the drug. The present study used bilateral ibotenic acid lesions to examine the role of the gustatory cortex in the suppression of CS intake induced by cocaine, morphine, and LiCl. The results show that bilateral lesions of the insular gustatory cortex (1) fully prevent the suppressive effects of both a 15 and a 30 mg/kg dose of morphine, (2) attenuate the suppressive effect of a 10 mg/kg dose of cocaine, but (3) are overridden by a 20 mg/kg dose of the drug. Finally, these same cortical lesions had no impact on LiCl-induced conditioned taste aversion. The current data show that the insular taste cortex plays an integral role in drug-induced avoidance of a gustatory CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned adrenocortical steroid elevations in the rat

An illness-induced taste aversion paradigm was used to condition an elevation in plasma corticosterone level. Rats were injected with cyclophosphamide 30 min after consuming a novel saccharin drinking solution. Plasma corticosterone levels were measured before conditioning to determine unconditioned steroid levels and 3 and 6 days after training when conditioned and nonconditioned animals were provided with the saccharin solution or plain water, or were left deprived. The pairing of saccharin and cyclophosphamide was effective in inducing a passive avoidance response. There were no differences between the steroid levels of conditioned and nonconditioned animals supplied with plain water or those that remained deprived, although deprivation increased corticosterone levels. Nonconditioned rats presented with saccharin had steroid levels that did not differ from control values. Conditioned animals presented with saccharin showed an elevation in steroid level which was significantly greater than that observed in any other group. Comparable results were obtained when LiCl was used as the unconditioned stimulus.     

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.     

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)     

Behaviorally functional opioid systems in infant rats: I. Evidence for olfactory and gustatory classical conditioning.

Conducted 2 series of experiments to characterize the behavioral function of opioid systems in neonatal rats. In the 1st series, the reinforcing properties of exogenous opioids were investigated in 112 5-day-old pups. Ss' ability to associate the novel taste of saccharin, received while suckling, with intraperitoneal morphine injections was assessed. Results show that Ss that received 0.5 ml of saccharin prior to morphine administration ingested considerably more saccharin on Day 10 than did control rats. The 2nd set of experiments was conducted to determine whether 144 rat pups could associate a novel odor with morphine administration. Five days after conditioning, that stimulus was highly preferred by morphine-treated Ss compared with saline control Ss. Thus positive associations were formed with either a novel taste stimulus experienced while suckling or with an odor experienced during social isolation. Conditioning was cue specific and was retained for at least 5 days. The formation of these associations was blocked with opioid antagonists given prior to conditioning. Data suggest behaviorally functional opioid receptors and raise the possibility of a functional role of the endogenous opioids in motivational processes in infant rats. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation of appetitive Pavlovian conditioning by d-amphetamine in the shell, but not the core, of the nucleus accumbens.

The effects of postsession d-amphetamine within subregions of the ventral and dorsal striatum on appetitive Pavlovian learning were assessed. Rats acquired a conditioned approach response on presentation of a stimulus predictive of 10% sucrose solution (unconditioned stimulus [US]), but not during equally frequent presentations of a stimulus uncorrelated with the US. In Experiment 1, postsession d-amphetarnine infusions enhanced acquisition of conditioned responding, with no effect on control measures. In Experiment 2, rats received postsession d-amphetamine in the accumbens shell or core. Shell infusions facilitated conditioning; core infusions did not. In Experiment 3, dorsomedial striatal infusions of d-amphetamine also were ineffective. In sum, dopaminergic activation within the shell, but not the core, of the nucleus accumbens facilitates the acquisition of a Pavlovian association. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparison of taste aversions induced by radiation and lithium chloride in CS-US and US-CS paradigms.

Describes 3 experiments with a total of 454 albino male Charles-River rats. Conditioned taste aversions induced by ionizing radiation and lithium chloride (LiCl) were compared with both forward (CS-UCS, conditioned stimulus-unconditioned stimulus) and backward (UCS-CS) conditioning paradigms. Taste aversions were produced when a saccharin CS preceded or followed a 100-r radiation UCS by as much as 6 hrs, but a 2%-of-body-weight, .15-mol LiCl UCS was effective only in CS-UCS pairings. It is argued that the ineffectiveness of an LiCl stimulus in UCS-CS pairings was not attributable to differences in the "strength" of the respective LiCl and radiation doses in that these doses yielded comparable aversions in forward pairings. These results are related to inadequacies of a "sickness" model of taste aversion conditioning. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased liking for a solution is not necessary for the attenuation of neophobia in rats.

Recent evidence suggests that liking and wanting of food rewards can be experimentally dissociated (e.g., Berridge, 1996); this dissociation extends to attenuated neophobia in the present study. Rats tend to eat less of a novel food than a familiar food, a phenomenon called neophobia. The present experiments evaluated whether attenuation of neophobia by prior exposure reflects enhanced liking of the flavor using the Taste Reactivity (TR) test. In Experiment 1, rats given five 10-s TR trials with water or various concentrations of saccharin solution (0.1%, 0.2%, 0.5%) did not show a change in the number of hedonic reactions displayed across trials. However, in a subsequent consumption test from a bottle containing 0.25% saccharin solution, rats with no prior saccharin exposure (group water) consumed less than rats with prior saccharin exposure; that is they displayed neophobia. In Experiment 2, whether rats received five 10-s TR trials with water or 0.5% saccharin solution, they did not display a difference in hedonic reactions to 0.25% saccharin solution in two 5-min TR test trials. These results suggest that the attenuation of neophobia is evidenced as an increase in the tendency to approach a bottle containing the flavored solution (wanting), but not as an enhanced liking of that solution. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Once is too much: Conditioned changes in accumbens dopamine following a single saccharin-morphine pairing.

The present study tested whether presentation of a taste cue would support conditioned suppression of dopamine in the nucleus accumbens (NAcc) following a single taste-drug pairing. Nondeprived male Sprague-Dawley rats were given 20-min access to a 0.15% saccharin conditioned stimulus (CS). Immediately thereafter, experimental rats were injected with morphine (15 mg/kg ip); standard controls were injected with saline; and explicitly unpaired controls were injected with morphine, but approximately 24 hr later. All rats were then given one 20-min CS-only test. Microdialysis samples from the NAcc were measured over 20-min intervals before, during, and after CS access on the conditioning and test trial. The results showed that a single saccharin-morphine pairing led to a marked reduction in CS intake, and the reduction in intake was accompanied by a conditioned blunting of the accumbens dopamine response to the saccharin reward cue. In turn, a single exposure to the saccharin cue also blunted the unconditioned dopamine response to morphine. Reward comparison effects, then, are cross-modal, bidirectional, and immediate, resulting in both unconditioned and conditioned changes in brain and behavior. (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)     

Within-compound learning with US presentation in taste aversion.

Determined whether the presentation of a LiCl unconditioned stimulus/stimuli (UCS) disrupts within-compound learning in a taste aversion preparation, using 30 male and 32 female rats in 3 experiments. In Exp I, Ss showed stronger associations between 2 solutions presented in a compound when the compound was followed by LiCl. Exp II showed that an immediate LiCl injection produced stronger flavor–flavor association than a delayed injection. Exp III provided a comparison with Ss that did not receive the treatment to enhance consumption of salty solutions. Results indicate that the effects of Exp II depended on the treatment that altered consumption of 1 component. (French abstract) (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.     

Environmental signals for ethanol enhance free-choice ethanol consumption.

The effect of cues associated with gastric infusion of ethanol on the free-choice consumption of ethanol was assessed in three experiments. In the first experiment, infusion of ethanol reduced ethanol consumption on a choice test between 10% ethanol and tap water, compared with saline. Drinking in the presence of drug-associated cues attenuated this ethanol-induced aversion. In the second experiment smaller doses of ethanol were used, and the consumption of a more palatable solution of ethanol (0.1% saccharin?+?10% ethanol) was compared with that of tap water. Prior infusion with ethanol enhanced the consumption of the sweetened ethanol, but only when drug-associated cues were present. The third experiment replicated this effect in animals that had extensive experience with the sweetened ethanol prior to infusion. These findings provide empirical evidence that Pavlovian conditioning contributes to drug-taking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Haloperidol attenuates rewarding and aversively conditioned suppression of saccharin solution intake: Reevaluation of the anhedonia hypothesis of dopamine blocking.

The dopamine (DA) antagonist, haloperidol, affected the conditioned suppression of a saccharin solution intake (the conditioned stimulus, CS) induced by amphetamine (AMPH) and lithium chloride (LiCl) unconditioned stimuli (USs). Four experiments showed that (a) haloperidol by itself did not reduce saccharin solution intake. (b) When haloperidol was injected between the CS and the US, the conditioned suppression was attenuated; however, (c) this did not occur when haloperidol was injected after the US, indicating that haloperidol affected the perception of the US. (d) This attenuation was found with both rewarding AMPH and aversive LiCl treatments, indicating that the valence of the US was unimportant. Thus, the so-called "anhedonia response" might be due to weakening of US impact. A general salient-stimulus hypothesis was proposed, with the anhedonia hypothesis of DA blocking as its subset. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Morphine-conditioned changes in locomotor activity: Role of the conditioned stimulus.

When a multisensory environment was reliably paired with morphine (2 mg/kg) in rats, that environment, in a drug-free test, evoked a hyperactive conditioned response (CR). When an olfactory cue (banana odor) was the only stimulus element reliably paired with morphine, it also elicited a hyperactive CR. However, a gustatory cue (saccharin solution) evoked a hypoactive CR. This taste-elicited decrease in activity was dose dependent; morphine at 2 and 4 mg/kg conditioned hypoactivity, whereas a higher dose (8 mg/kg) did not. A robust conditioned saccharin aversion occurred only at the highest dose of morphine, suggesting disassociation between the hypoactive CR and taste aversion. A taste cue present during context conditioning also prevented either acquisition or expression of the hyperactive CR to the context. The modality of the conditioned stimulus is a critical determinant of the form of the CR in a morphine locomotor conditioning paradigm. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The suppressive effects of sucrose and cocaine, but not lithium chloride, are greater in Lewis than in Fischer rats: Evidence for the reward comparison hypothesis.

Rats suppress intake of a saccharin conditioned stimulus (CS) when it is paired with an aversive unconditioned stimulus (UCS), an appetitive UCS, or a drug of abuse such as morphine or cocaine. It is unclear, however, whether the reduction in intake induced by these drugs is mediated by their aversive or their rewarding properties. The present set of experiments addressed this question by comparing the suppressive effects of a known aversive UCS (LiCl), a known reinforcing UCS (sucrose), and a drug of abuse (cocaine) in two strains of rats (i.e., Lewis and Fischer 344 rats) that differ in their preference for rewarding stimuli. The results show that, although both strains readily acquired a LiCl-induced conditioned taste aversion (CTA), the suppressive effects of sucrose and cocaine were robust in the drug-preferring Lewis rats and absent in the Fischer rats. These data argue against a CTA account and in favor of the reward comparison hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)