Behavioral and neural correlates of licking for 66% alcohol in Wistar rats: Caloric balance or sensation/novelty seeking?

Whereas rodents generally reject high alcohol concentrations, access to 66% alcohol can reinforce operant licking in a progressive ratio situation. Three experiments were conducted to identify a potential mechanism underlying this effect. In Experiment 1, food-restricted male and female Wistar rats received access to either 66% alcohol or water in their home cage for one hour over four sessions. Consumption of alcohol and water was similar, showing that rats neither preferred nor rejected 66% alcohol. Peripheral (but not central) activity in an open field (OF) was higher after access to 66% alcohol than water, a result inconsistent with motor impairment. Blood alcohol concentration was higher after 66% alcohol than water and was positively correlated with fluid displacement and peripheral distance in the OF. c-Fos immunoreactivity after exposure to 66% alcohol vs. water showed increased activation in the nucleus accumbens shell, anterior cingulate cortex, and insular cortex. In Experiment 2, whether access to food was restricted (to an 81-84% of the ad libitum weight) or free (ad libitum), female Wistar rats licked at similar frequency from a sipper tube delivering 66% alcohol. This result is inconsistent with an account based on the caloric content of 66% alcohol. In Experiment 3, food-restricted male and female Wistar rats exhibited a positive correlation between activity in the central area of an OF (an index of sensation/novelty seeking) and licking for 66% alcohol. These results are consistent with the hypothesis that the reinforcing value of 66% alcohol is related to sensation/novelty seeking.

Frustrative nonreward and the basal ganglia: Chemogenetic inhibition and excitation of the nucleus accumbens and globus pallidus externus during reward downshift.

Frustrative nonreward contributes to anxiety disorders and addiction, and is included in the Research Domain Criteria initiative as a relevant endophenotype. These experiments explored the role of the basal ganglia in consummatory reward downshift (cRD) using inhibitory and excitatory DREADDs (designer receptors exclusively activated by designer drugs) infused in either the nucleus accumbens (NAc) or one of its downstream targets, the globus pallidus externus (GPe). NAc inhibition did not disrupt consummatory suppression during a 32-to-2% (Experiment 1) or 8-to-2% sucrose downshift (Experiment 2). However, NAc excitation enhanced consummatory suppression during a 32-to-2% sucrose downshift (Experiment 1). GPe inhibition caused a trend toward increased consummatory suppression after a 32-to-2% sucrose downshift, whereas GPe excitation eliminated consummatory suppression after an 8-to-2% sucrose downshift (Experiment 3). Chemogenetic manipulations of NAc and GPe had no detectable effects on open field activity. The effects of DREADD activation via clozapine N-oxide (CNO) administration were compared to controls that carried the DREADDs, but received vehicle injections. There was no evidence that CNO or vehicle injections in virus vector control (VVC) animals affected cRD or OF activity after either CNO or vehicle injections. NAc and GPe excitation led to opposite results in the cRD task, providing evidence that the basal ganglia circuit has a function in frustrative nonreward in the absence of detectable motor effects.

Cetacean responses to violation of expectation paradigm in a free-swim context.

The investigation of individual responses to unexpected stimuli or outcomes provides insights into basic cognitive processes, such as mental representations, emotional states of surprise, and detections of anomalies. Three experiments using a violation of expectation paradigm were conducted with 12 belugas and 17 bottlenose dolphins in managed care to test two classes of stimuli (humans and objects) in manipulated sequences of familiar and unfamiliar humans (Study 1, trainers and strangers), familiar and unfamiliar objects (Study 2, typical enrichment devices and new objects), and finally objects and humans (Study 3). Gaze durations were assessed for each condition in a given study during free-swim contexts. The results supported previous findings that visual stimuli, regardless of class, were stimulating and intriguing for both belugas and bottlenose dolphins. Belugas were more likely to gaze longer at human and object stimuli and tended to gaze longer at unexpected experiences than control or expected experiences. Bottlenose dolphins showed similar trends except when objects were involved. Individual variability was present for both species with some individuals showing stronger patterns of responses for expected experiences than others. After 2 years of intermittent experiments, belugas and bottlenose dolphins in managed care maintained their curiosity about visual stimuli, for which they received no primary reinforcement. Investigating responses to unexpected stimuli with animals in managed care may provide insight into how these animals respond to biologically relevant conditions, such as boat presence, predators, and unfamiliar conspecifics.

Incentive disengagement and the adaptive significance of frustrative nonreward.

Mammals respond to an unexpected reward omission or reduction with a variety of behavioral and physiological responses consistent with an aversive emotion traditionally called frustrative nonreward. This review focuses on two aspects of frustrative nonreward, namely (1) the evidence for an aversive emotional state activated by the surprising omission or reduction of a rewarding outcome, and (2) the adaptive value of frustration. Frustrative nonreward has been mainly studied in terms of its mechanisms, across development in rats and across vertebrate species in comparative research. However, its adaptive function remains obscure. Following Domjan's approach to animal learning, this article explores a specific adaptive function hypothesis of frustrative nonreward called the incentive disengagement hypothesis. According to this hypothesis, the adaptive function of frustrative nonreward is to break an attachment to a site, situation, or stimulus that no longer yields appetitive resources (especially food and fluids) to promote the search for rewards in alternative locations. This function is of particular relevance given that mammals are especially vulnerable to reward loss due to their high metabolic rate and the energy demands of their relatively large brain.

Frustrative nonreward and cannabinoid receptors: Chronic (but not acute) WIN 55,212-2 treatment increased resistance to change in two reward downshift tasks.

Assessing the role of cannabinoid (CB) receptors in behavior is relevant given the trend toward the legalization of medicinal and recreational marijuana. The present research aims at bridging a gap in our understanding of CB-receptor function in animal models of frustrative nonreward. These experiments were designed to (1) determine the effects of chronic administration of the nonselective CB1-receptor agonist WIN 55,212-2 (WIN) on reward downshift in rats and (2) determine whether the effects of chronic WIN were reducible to acute effects. In Experiment 1, chronic WIN (7 daily injections, 10 mg/kg, ip) accelerated the recovery of consummatory behavior after a 32-to-4% sucrose downshift relative to vehicle controls. In addition, chronic WIN eliminated the preference for an unshifted lever when the other lever was subject to a 12-to-2 pellet downshift in free-choice trials, but only in animals with previous experience with a sucrose downshift. In Experiment 2, acute WIN (1 mg/kg, ip) reduced consummatory behavior, but did not affect recovery from a 32-to-4% sucrose downshift. The antagonist SR 141716A (3 mg/kg, ip) also failed to interfere with recovery after the sucrose downshift. In Experiment 3, acute WIN administration (1 mg/kg, ip) did not affect free-choice behavior after a pellet downshift, although it reduced lever pressing and increased magazine entries relative to vehicle controls. The effects of chronic WIN on frustrative nonreward were not reducible to acute effects of the drug. Chronic WIN treatment in rats, like chronic marijuana use in humans, seems to increase resistance to the effects of frustrative nonreward.

Frustrative nonreward: Chemogenetic inactivation of the central amygdala abolishes the effect of reward downshift without affecting alcohol intake.

The role of the central amygdala (CeA) in the adjustment to a 32-to-2% sucrose downshift in the consummatory successive negative contrast (cSNC) task and in a free-choice 10% alcohol-water preference task (PT) was studied using chemogenetic inactivation. cSNC is a model of frustrative nonreward that enhances alcohol consumption. In Experiment 1, sessions 1-10 involved 5-min access to 32% sucrose and sessions 11-12 involved access to 2% sucrose. Vehicle or clozapine N-oxide (CNO; 1 or 3 mg/kg, ip), used later to activate the inhibitory designer receptor, was administered 30 min before sessions 11-12. There was no evidence that CNO affected consummatory behavior after the sucrose downshift. In Experiment 2, all animals received an infusion of the inhibitory designer receptor hM4D(Gi) into the CeA. After recovery, animals received access to either 32% or 2% sucrose on sessions 1-10, followed by 2% sucrose on sessions 11-12. Immediately after each 5-min sucrose session, animals received a 2-bottle, 1-h PT with 10% alcohol and water. CNO (3 mg/kg, ip) or vehicle was administered 30 min before sessions 11-12. CeA inactivation prior to sucrose downshift eliminated the cSNC effect, which was observed in vehicle controls. However, there was no evidence that CeA inactivation affected preference for 10% alcohol over water. These results support the hypothesis that CeA activity is critical for cSNC effect, an outcome consistent with the view that the amygdala plays a central role in frustrative nonreward.

Preliminary observations of an unusual mouth interaction between beluga calves (Delphinapterus leucas).

Although many animals, including odontocetes, exhibit interactions involving mouths (e.g., mouthing, nuzzling, biting), a limited number of animals display mouth-to-mouth social interactions that involve mutual coordination and collaboration. The purpose of this paper is to describe briefly a spontaneous and unexpected mouth-to-mouth social interaction between beluga calves in human care during their first year of life. Forty-seven independent events were identified after event sampling from more than 345 hr of observations of four mother-calf pairs and their companions. Unique aspects of this behavior included early emergence presumably without the benefit of a model and a preference for similar aged partners. Adult belugas did not display this social interaction. Based on its early emergence, the presence of similar-aged partner preferences, and affiliative cooperative contexts, this unusual mouth-to-mouth social interaction may play a significant role in beluga social and physical development. To evaluate this possibility, additional research is needed in which the complete topography, possible functions, and potential outcomes associated with this rare but conspicuous behavior exhibited by beluga calves are assessed.

Responses to familiar and unfamiliar objects by belugas (Delphinapterus leucas), bottlenose dolphins (Tursiops truncatus), and Pacific white-sided dolphins (Lagenorhynchus obliquidens).

Previous research with bottlenose dolphins (Tursiops truncatus) demonstrated their ability to discriminate between familiar and unfamiliar stimuli. Dolphins gazed longer at unfamiliar stimuli. The current study attempted to extend this original research by examining the responses of three species of cetaceans to objects that differed in familiarity. Eleven belugas from two facilities, five bottlenose dolphins and five Pacific white-sided dolphins housed at one facility were presented different objects in a free-swim scenario. The results indicated that the animals gazed the longest at unfamiliar objects, but these gaze durations did not significantly differ from gaze durations when viewing familiar objects. Rather, the animals gazed longer at unfamiliar objects when compared to the apparatus alone. Species differences emerged with longer gaze durations exhibited by belugas and bottlenose dolphins and significantly shorter gaze durations for Pacific white-sided dolphins. It is likely that the animals categorized objects into familiar and unfamiliar categories, but the free-swim paradigm in naturalistic social groupings did not elicit clear responses. Rather this procedure emphasized the importance of attention and individual preferences when investigating familiar and unfamiliar objects, which has implications for cognitive research and enrichment use.

Lateralized swim positions are conserved across environments for beluga (Delphinapterus leucas) mother-calf pairs.

Research with wild belugas has indicated that, during mother-calf swims, calves spend more time on their mothers' right side, which enables the calves to maintain visual contact with their mothers using their left eye. This bias may facilitate processing of social information by the right hemisphere, much like human and non-human primates and other animals. The current study explored the social laterality of the Cook Inlet, AK beluga population in comparison to a beluga population in managed care. As expected, the results indicated that the calves spent more time on the mothers' right side than the left for both populations. We also examined the developmental trend for the belugas in managed care and found that the calves generally preferred to swim on their mother's right side across most months, although there was an inversion during the third quarter when a left-side preference appeared. Individual differences were present. The results corroborate previous research conducted with two wild beluga populations from the White Sea and from the Sea of Okhotsk in which a left-eye bias was displayed by calves when swimming with their mothers. In conclusion, a preference for a lateralized swim position appears to be conserved across wild and managed care settings, and this lateralized swim position may facilitate the processing of social information or familiar stimuli for the calves.

Development of sociality and emergence of independence in a killer whale (Orcinus orca) calf from birth to 36 months.

Dolphin calves spend most of their time swimming with their mother immediately after birth. As they mature, the calves become increasingly independent, and begin to interact more often with other calves, juveniles, and sub-adults. For bottlenose dolphin calves, sociality is related to maternal behaviors. Unfortunately, much less is known about the development of sociality and emergence of independence for killer whale calves. The purpose of this study was to examine the developmental changes in social behaviors and solitary activities of a killer whale calf across a 36-month period. Focal follow video recordings of a mother-calf pair housed at SeaWorld San Antonio were collected 2-6 times a day for 5-15 min at 6-month intervals. Using a sample of randomly selected video recordings at each month, developmental changes in swims and social interactions with her mother, swims and social interactions with non-maternal partners, and solitary activities (e.g., solitary swims, solitary play) were observed across the months. The calf spent most of her time swimming with the mother across the 36-month period. The time the calf socialized with her mother was greater than the time she socialized with others at each month. Besides her mother, the calf socialized more often with the other adult female compared to adult males. As the calf matured, the increase in the time she spent socializing with adult killer whales other than the mother corresponded with an increase in the rate and time spent in solitary play. The developmental trends of sociality and emerging independence replicate research conducted with calves of other dolphin species. Zoo Biol. 36:11-20, 2017. © 2016 Wiley Periodicals, Inc.

Gastrointestinal sensitivity and gastroesophageal reflux disease.

This paper reports on gastrointestinal sensitivity, including on the role of refluxate volume on the perception of reflux symptoms; experimental pain models that mimic mechanisms and symptoms of pain associated with esophageal diseases; the potential role of the acid receptor TRPV1 in the genesis of gastroesophageal reflux disease (GERD) symptoms; and roles for ATP and the purine and pyrimidine receptor subfamilies P1, P2X, and P2Y in the pathogenesis of GERD symptoms.