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 sec 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 sec 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

Monoacylglycerol lipase inhibition attenuates acute and anticipatory nausea in rats

This study investigates the role of the endocannabinoid 2-arachidonyl glycerol (2-AG) in regulating acute and anticipatory nausea in rats using the conditioned gaping model. The animals were systemically pretreated with MJN110, a selective monoacylglycerol lipase (MAGL) inhibitor, to enhance endogenous levels of 2-AG. Acute nausea was assessed using the taste reactivity model in which a flavour, saccharin, was paired with the administration of the emetic agent, lithium chloride (LiCl). Anticipatory nausea was assessed using a model of contextually elicited conditioned gaping in which a context was paired with the emetic agent, LiCl. Results indicated that MJN110 at the 10.0 mg kg-1 and 20.0 mg kg-1 dosage significantly attenuated acute and anticipatory nausea, as displayed by the significant reduction in mean number of gapes. This suppression was mediated by CB1 receptor activation as displayed by reversal of such effects when MJN110 was coadministered with the CB1 receptor antagonist, SR 141716. The results suggest that enhancement of endogenous 2-AG levels by MAGL inhibition may have anti-emetic potential. Keywords: 2-arachidonyl glycerol; monoacylglycerol lipase; endocannabinoid; nausea; conditioned gaping; CB1 recepto

The effect of cannabidiol and URB597 on conditioned gaping (a model of nausea) elicited by a lithium-paired context in the rat.

RationaleAnticipatory nausea (AN) experienced by chemotherapy patients is resistant to current anti-nausea treatments. In this study, the effect of manipulation of the endocannabinoid (EC) system on a rat model of nausea (conditioned gaping) was determined.ObjectiveThe potential of cannabidiol (CBD) and the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (URB) to reduce conditioned gaping in rats were evaluated.Materials and methodsIn each experiment, rats received four conditioning trials in which they were injected with lithium chloride immediately before placement in a distinctive odor-laced context. During testing, in experiment 1, rats were injected with vehicle (VEH), 1, 5 or 10 mg/kg CBD 30 min before placement in the context previously paired with nausea and in experiment 2, rats were injected with VEH, 0.1 or 0.3 mg/kg URB 2 h before placement in the context. Additional groups evaluated the ability of the CB(1) antagonist/inverse agonist, SR141716A, to reverse the suppressive effects of URB. Experiment 3 measured the potential of URB to interfere with the establishment of conditioned gaping.ResultsWhen administered before testing, CBD (1 and 5, but not 10 mg/kg) and URB (0.3, but not 0.1 mg/kg) suppressed conditioned gaping. The effect of URB was reversed by pre-treatment with the CB(1) antagonist/inverse agonist, SR141716A. When administered before conditioning, URB also interfered with the establishment of conditioned gaping.ConclusionsManipulations of the EC system may have therapeutic potential in the treatment of AN

The effect of cannabidiol and URB597 on conditioned gaping (a model of nausea) elicited by a lithium-paired context in the rat.

RationaleAnticipatory nausea (AN) experienced by chemotherapy patients is resistant to current anti-nausea treatments. In this study, the effect of manipulation of the endocannabinoid (EC) system on a rat model of nausea (conditioned gaping) was determined.ObjectiveThe potential of cannabidiol (CBD) and the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (URB) to reduce conditioned gaping in rats were evaluated.Materials and methodsIn each experiment, rats received four conditioning trials in which they were injected with lithium chloride immediately before placement in a distinctive odor-laced context. During testing, in experiment 1, rats were injected with vehicle (VEH), 1, 5 or 10 mg/kg CBD 30 min before placement in the context previously paired with nausea and in experiment 2, rats were injected with VEH, 0.1 or 0.3 mg/kg URB 2 h before placement in the context. Additional groups evaluated the ability of the CB(1) antagonist/inverse agonist, SR141716A, to reverse the suppressive effects of URB. Experiment 3 measured the potential of URB to interfere with the establishment of conditioned gaping.ResultsWhen administered before testing, CBD (1 and 5, but not 10 mg/kg) and URB (0.3, but not 0.1 mg/kg) suppressed conditioned gaping. The effect of URB was reversed by pre-treatment with the CB(1) antagonist/inverse agonist, SR141716A. When administered before conditioning, URB also interfered with the establishment of conditioned gaping.ConclusionsManipulations of the EC system may have therapeutic potential in the treatment of AN

Orally Administered <i>N</i>-Oleoyl Alanine Blocks Acute Opioid Withdrawal Induced-Conditioned Place Preference and Attenuates Somatic Withdrawal following <i>Chronic</i> Opioid Exposure in Rats

(1) Background: Intraperitoneal injections of the endogenous N-acyl amino acid N-Oleoyl alanine (OlAla) effectively reduces both the affective and somatic responses produced by opioid withdrawal in preclinical models. To increase the translational appeal of OlAla in clinical drug applications, the current experiments tested whether oral OlAla pretreatment also attenuates opioid withdrawal in rats. (2) Methods: In Experiment 1, to assess its impact on affective withdrawal behavior, OlAla (0, 5, 20 mg/kg) was orally administered during the conditioning phase of an acute naloxone-precipitated morphine withdrawal conditioned place avoidance task. In Experiment 2, to assess its impact on somatic withdrawal behavior, OlAla (5–80 mg/kg) was orally administered prior to naloxone-precipitated withdrawal from chronic heroin exposure. (3) Results: Pretreatment with oral OlAla at the higher (20 mg/kg), but not lower (5 mg/kg) dose, reduced the establishment of an acute morphine withdrawal-induced conditioned place aversion. Instead, the lower dose of oral OlAla (5 mg/kg) reduced heroin withdrawal-induced abdominal contractions and diarrhea, whereas higher doses were without effect. (4) Conclusions: The results suggest a dose-dependent reduction of opioid withdrawal responses by orally administered OlAla, and further highlight the potential utility of this compound for opioid withdrawal in clinical populations

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 sec 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 sec 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

Effects of post-training heroin and d-amphetamine on consolidation of win-stay learning and fear conditioning

It has been proposed that the reinforcing properties of drugs of abuse are due, in part, to their ability to enhance memory consolidation. To test this hypothesis, heroin (0.03-3 mg/kg, SC) and d-amphetamine (0.5-2 mg/kg, SC) were administered to male Sprague-Dawley rats immediately or 4 h after training on win-stay and fear conditioning tasks. On the win-stay, immediate post-training administration of lower doses of heroin and d-amphetamine enhanced acquisition, and probe tests further revealed that these drugs enhanced different aspects of learning. Higher doses had no effect or impaired performance, particularly when administered repeatedly. On fear conditioning, the memory-enhancing effects of immediate post-training administration of lower heroin and d-amphetamine doses were revealed o

Latent inhibition of conditioned disgust reactions in rats

The present experiments, using the latent inhibition (LI) paradigm, evaluated the effect of nonreinforced exposure to saccharin on the acquisition of an LiCl-induced saccharin aversion as measured by conditioned disgust reactions in the taste reactivity test and conditioned taste avoidance in a consumption test. When rats were preexposed to saccharin by bottle exposure (Experiments 1 and 3), LI was evidenced only by conditioned taste avoidance (bottle testing), but not by conditioned disgust reactions (intraoral [IO] testing). On the other hand, when rats were preexposed to saccharin by IO infusion (Experiments 2 and 3), LI was evidenced only by conditioned disgust reactions, but not by conditioned taste avoidance. Experiment 4 showed that LI of conditioned disgust reactions does not appear to be affected by a context shift from preexposure to testing phases. These results show that the expression of LI of both conditioned taste avoidance and conditioned disgust reactions depends critically on a common method of flavor exposure during preexposure and testing