Interlick Interval Research Articles

Further disentangling the motivational processes underlying benzodiazepine hyperphagia

In addition to their well-known anxiolytic functions, benzodiazepines produce hyperphagia. Previously, we reported that the benzodiazepine, chlordiazepoxide (CDP), increased consumption of both normally-preferred and normally-avoided taste stimuli during long-term (1 h) tests, primarily through changes in licking microstructure patterns associated with hedonic taste evaluation, whereas there was little effect on licking microstructure measures associated with post-ingestive feedback. In this study, we further examined the hedonic and motivational specificity of CDP effects on ingestive behavior. We tested brief access (15 s) licking responses for tastants spanning all taste qualities after treatment with either CDP (5 or 10 mg/kg) or the non-benzodiazepine anxiolytic, buspirone (1.5 or 3 mg/kg). A between-subjects, counterbalanced design compared the CDP or buspirone effects on licking responses for water and a range of weak to strong concentrations of NaCl, Q-HCl, citric acid, MSG, saccharin, and capsaicin under water-restricted (23 h) conditions; and sucrose, saccharin, and MSG under water-replete conditions. In a dose dependent manner, CDP increased licking for taste stimuli that were normally-avoided after saline treatment, with a notable exception observed for the trigeminal stimulus, capsaicin, which was not affected at any concentration or drug dose, suggesting a taste-specific effect of CDP on orosensory processing. Under water-replete conditions, CDP dose-dependently increased licking to normally-accepted concentrations of sucrose, saccharin, and MSG. There was no effect of either drug on licks for water under either water-restricted or water-replete conditions. Buspirone slowed oromotor coordination by increasing brief interlick intervals, but it did not affect licking for any concentrations of the tastants. Overall, these results indicate that benzodiazepines selectively enhance the hedonic acceptance of gustatory orosensory stimuli, independent of general anxiolytic or oromotor coordination effects, or physiological states such as thirst.

Acute effects of radiation treatment to submental muscles on burrowing and swallowing behaviors in a rat model.

Swallowing impairments are a major complication of radiation treatment for oropharyngeal cancers, influencing oral intake and quality of life. The timing and functional consequences of radiation treatment on the swallowing process is not clearly understood. A rodent radiation injury model was used to investigate the onset of oral and pharyngeal dysfunctions in deglutition related to radiation treatment. This study tested the hypothesis that (Wall et al., 2013) alterations in normal biting, licking, and swallowing performance would be measurable following 64Gy of fractionated radiation to the submental muscles; and (Kotz et al., 2004) radiation will affect the animal’s general well-being as measured via burrowing activity. Seven rats received radiation using a clinical linear accelerator given in 8 fractions of 8Gy and another seven animals received sham anesthesia only treatment. Swallowing bolus transit/size was assessed via videofluoroscopy, tongue movement during drinking was measured via an electrical lick sensor, and biting was analyzed from acoustic recordings of a vermicelli pasta test. Burrowing activity was measured by the amount of gravel substrate displaced within a container. Measurements were taken at baseline, during treatment (1–4 weeks), and after completion of treatment (weeks 5 & 6). Decreases in licking frequency and increases in inter-lick interval were observed 5- and 6-weeks post-treatment. Significant decreases in burrowing performance, swallowing frequency, and inter-swallow interval were observed starting the last week of treatment and continuing up to 2-weeks after completion. Results suggest that tongue dysfunction is one of the first treatment related feeding problems to present immediately after the completion of radiation to the submental muscles.

Pilot Study of the Effects of Chronic Intracerebroventricular Infusion of Human Anti-IgLON5 Disease Antibodies in Mice.

Background: Anti-IgLON5 disease is a rare late-onset neurological disease associated with autoantibodies against IgLON5, neuronal accumulation of phosphorylated Tau protein (p-Tau), and sleep, respiratory, and motor alterations. Purpose: We performed a pilot study of whether the neuropathological and clinical features of anti-IgLON5 disease may be recapitulated in mice with chronic intracerebroventricular infusion of human anti-IgLON5 disease IgG (Pt-IgG). Methods: Humanized transgenic hTau mice expressing human Tau protein and wild-type (WT) control mice were infused intracerebroventricularly with Pt-IgG or with antibodies from a control subject for 14 days. The sleep, respiratory, and motor phenotype was evaluated at the end of the antibody infusion and at least 30 days thereafter, followed by immunohistochemical assessment of p-Tau deposition. Results: In female hTau and WT mice infused with Pt-IgG, we found reproducible trends of diffuse neuronal cytoplasmic p-Tau deposits in the brainstem and hippocampus, increased ventilatory period during sleep, and decreased inter-lick interval during wakefulness. These findings were not replicated on male hTau mice. Conclusion: The results of our pilot study suggest, but do not prove, that chronic ICV infusion of mice with Pt-IgG may elicit neuropathological, respiratory, and motor alterations. These results should be considered as preliminary until replicated in larger studies taking account of potential sex differences in mice.

Persistent Feeding and Swallowing Deficits in a Mouse Model of 22q11.2 Deletion Syndrome.

Disrupted development of oropharyngeal structures as well as cranial nerve and brainstem circuits may lead to feeding and swallowing difficulties in children with 22q11. 2 deletion syndrome (22q11DS). We previously demonstrated aspiration-based dysphagia during early postnatal life in the LgDel mouse model of 22q11DS along with disrupted oropharyngeal morphogenesis and divergent differentiation and function of cranial motor and sensory nerves. We now ask whether feeding and swallowing deficits persist in adult LgDel mice using methods analogous to those used in human patients to evaluate feeding and swallowing dysfunction. Compared to wild-type mice, videofluoroscopic swallow study revealed that LgDel mice have altered feeding and swallowing behaviors, including slower lick rates, longer inter-lick intervals, and longer pharyngeal transit times with liquid consistency. Transoral endoscopic assessment identified minor structural anomalies of the palate and larynx in one-third of the LgDel mice examined. Video surveillance of feeding-related behaviors showed that LgDel mice eat and drink more frequently. Furthermore, LgDel animals engage in another oromotor behavior, grooming, more frequently, implying that divergent craniofacial and cranial nerve structure and function result in altered oromotor coordination. Finally, LgDel mice have significantly increased lung inflammation, a potential sign of aspiration-based dysphagia, consistent with results from our previous studies of early postnatal animals showing aspiration-related lung inflammation. Thus, oromotor dysfunction, feeding, and swallowing difficulties and their consequences persist in the LgDel 22q11DS mouse model. Apparently, postnatal growth and/or neural plasticity does not fully resolve deficits due to anomalous hindbrain, craniofacial, and cranial nerve development that prefigure perinatal dysphagia in 22q11DS. This new recognition of persistent challenges with feeding and swallowing may provide opportunities for improved therapeutic intervention for adolescents and adults with 22q11DS, as well as others with a history of perinatal feeding and swallowing disorders.

The Effect of Methylphenidate on the Microstructure of Schedule-Induced Polydipsia in an animal model of ADHD

Schedule-induced polydipsia (SIP) was established in spontaneously hypertensive rats (SHR), Wistar Kyoto rats (WKY), and Wistar rats, using a multiple fixed-time (FT) schedule of food delivery, with 30- and 90-s components. Thereafter, animals were exposed to methylphenidate (MPH; 2.5mg/kg/d) for six consecutive SIP sessions. A test to assess possible sensitization effects was also conducted four days after termination of the drug treatment. At baseline, FT 90-s produced longer and more frequent drinking episodes in SHR than in WKY. An analysis of the distribution of inter-lick intervals revealed that drinking was organized in bouts, which were shorter in SHR than in WKY. Across strains and schedules, MPH shifted drinking episodes towards the beginning of inter-food intervals, which may reflect a stimulant effect on SIP. MPH transiently reduced the frequency of drinking episodes in WKY in FT 30-s, and more permanently reduced the frequency of licking bouts in Wistar rats. MPH also increased the length of licking bouts in Wistar rats. Overall, SHR displayed a hyperactive-like pattern of drinking (frequent but short bouts), which 2.5mg/kg MPH appears to reduce in WKY and Wistar but not in SHR rats. It appears that therapeutic effects of MPH on hyperactive-like SIP require higher doses in SHR relative to control strains.

Genetic control of oromotor phenotypes: A survey of licking and ingestive behaviors in highly diverse strains of mice

In order to examine genetic influences on fluid ingestion, 20-min intake of either water or 0.1M sucrose was measured in a lickometer in 18 isogenic strains of mice, including 15 inbred strains and 3 F1 hybrid crosses. Intake and licking data were examined at a number of levels, including lick rate as defined by mean or median interlick interval, as well as several microstructural parameters (i.e. burst-pause structure). In general, strain variation for ingestive phenotypes were correlated across water and sucrose in all strains, indicating fundamental, rather than stimulus-specific, mechanisms of intake. Strain variation was substantial and robust, with heritabilities for phenotypes ranging from 0.22 to 0.73. For mean interlick interval (MPI; a measure of lick rate) strains varied continuously from 94.3 to 127.0ms, a range consistent with previous studies. Furthermore, variation among strains for microstructural traits such as burst size and number suggested that strains possess different overall ingestive strategies, with some favoring more short bursts, and others favoring fewer, long bursts. Strains also varied in cumulative intake functions, exhibiting both linear and decelerated rates of intake across the session.

Stress and Sucrose Intake Modulate Neuronal Activity in the Anterior Hypothalamic Area in Rats.

The anterior hypothalamic area (AHA) is an important integrative relay structure for a variety of autonomic, endocrine, and behavioral responses including feeding behavior and response to stress. However, changes in the activity of the AHA neurons during stress and feeding in freely moving rats are not clear. The present study investigated the firing rate and burst activity of neurons in the central nucleus of the AHA (cAHA) during sucrose intake in non-stressful conditions and after acute stress in freely behaving rats. Rats were implanted with micro-electrodes into the cAHA, and extracellular multi-unit activity was recorded during 1-h access to 10% sucrose in non-stressful conditions or after acute foot shock stress. Acute stress significantly reduced sucrose intake, total sucrose lick number, and lick frequency in licking clusters, and increased inter-lick intervals. At the cluster start (CS) of sucrose licking, the cAHA neurons increased (CS-excited, 20% of the recorded neurons), decreased (CS-inhibited, 42% of the neurons) or did not change (CS-nonresponsive, 38% of the neurons) their firing rate. Stress resulted in a significant increase in the firing rate of the CS-inhibited neurons by decreasing inter-spike intervals within the burst firing of these neurons. This increase in the stress-induced firing rate of the CS-inhibited neurons was accompanied by a disruption of the correlation between the firing rate of CS-inhibited and CS-nonresponsive neurons that was observed in non-stressful conditions. Stress did not affect the firing rate of the CS-excited and CS-nonresponsive neurons. However, stress changed the pattern of burst firing of the CS-excited and CS-nonresponsive neurons by decreasing and increasing the burst number in the CS-excited and CS-nonresponsive neurons, respectively. These results suggest that the cAHA neurons integrate the signals related to stress and intake of palatable food and play a role in the stress- and eating-related circuitry.

Temporal and qualitative dynamics of conditioned taste aversions in C57BL/6J and DBA/2J mice self-administering LiCl

Self-administration of LiCl solution has been shown to result in the formation of a conditioned taste aversion (CTA) that generalizes to NaCl in rats. This paradigm may have considerable ecological validity as it models CTA learning in natural settings, and also allows for the investigation of drinking microstructure as an assay of potential shifts in stimulus palatability. We used this paradigm to examine possible mouse strain differences in CTA acquisition, generalization, and extinction. In the first experiment, C57BL/6J (B6) and DBA/2J (D2) mice self-administered LiCl (or control NaCl) over a 20-minute free access acquisition period and were tested on the following day with a panel of taste solutions available in brief (5-s) trials delivered in random order. In the second experiment, mice again self-administered LiCl or NaCl (at low, 0.12M, or high, 0.24M concentrations) in a 20-minute session, and on the following day received a 20-minute free access period to equimolar NaCl. Strain differences were found for aspects of ingestive behavior, with B6 mice showing greater consumption of all stimuli, including water, while D2 mice lick faster, in less frequent but longer bursts. We did not, however, find evidence of a robust strain difference in taste aversion learning. Both strains demonstrated profound alterations in licking microstructure in the generalization session relative to controls. We suggest that a decrease in “lick efficiency” (the percentage of inter-lick intervals within a burst of short duration vs. longer duration) reflects avoidance behavior, and signals a shift in palatability of a stimulus following CTA.

Elevated dopamine alters consummatory pattern generation and increases behavioral variability during learning.

The role of dopamine in controlling behavior remains poorly understood. In this study we examined licking behavior in an established hyperdopaminergic mouse model—dopamine transporter knockout (DAT KO) mice. DAT KO mice showed higher rates of licking, which is due to increased perseveration of licking in a bout. By contrast, they showed increased individual lick durations, and reduced inter-lick intervals. During extinction, both KO and control mice transiently increased variability in lick pattern generation while reducing licking rate, yet they showed very different behavioral patterns. Control mice gradually increased lick duration as well as variability. By contrast, DAT KO mice exhibited more immediate (within 10 licks) adjustments—an immediate increase in lick duration variability, as well as more rapid extinction. These results suggest that the level of dopamine can modulate the persistence and pattern generation of a highly stereotyped consummatory behavior like licking, as well as new learning in response to changes in environmental feedback. Increased dopamine in DAT KO mice not only increased perseveration of bouts and individual lick duration, but also increased the behavioral variability in response to the extinction contingency and the rate of extinction.

The medial prefrontal cortex is crucial for the maintenance of persistent licking and the expression of incentive contrast.

We examined the role of the medial prefrontal cortex (mPFC) in reward processing and the control of consummatory behavior. Rats were trained in an operant licking procedure in which they received alternating access to solutions with relatively high and low levels of sucrose (20 and 4%, w/v). Each level of sucrose was available for fixed intervals of 30 s over 30 min test sessions. Over several days of training, rats came to lick persistently when the high level of sucrose was available and suppressed licking when the low level of sucrose was available. Pharmacological inactivations of the mPFC, specifically the rostral part of the prelimbic area, greatly reduced intake of the higher value fluid and only slightly increased intake of the lower value fluid. In addition, the inactivations altered within-session patterns and microstructural measures of licking. Rats licked equally for the high and low levels of sucrose at the beginning of the test sessions and “relearned” to reduce intake of the low value fluid over the test sessions. Durations of licking bouts (clusters of licks with inter-lick intervals <0.5 s) were reduced for the high value fluid and there were many more brief licking bouts (<1 s) when the low value fluid was available. These effects were verified using an alternative approach (optogenetic silencing using archaerhodopsin) and were distinct from inactivation of the ventral striatum, which simply increased overall intake. Our findings suggest that the mPFC is crucial for the maintenance of persistent licking and the expression of learned feeding strategies.

The Fine Temporal Structure of the Rat Licking Pattern: What Causes the Variabiliy in the Interlick Intervals and How is it Affected by the Drinking Solution?

Licking is a repetitive behavior controlled by a central pattern generator. Even though interlick intervals (ILIs) within bursts of licks are considered fairly regular, the conditions that affect their variability are unknown. We analyzed the licking pattern in rats that licked water, 10% sucrose solution, or 10% ethanol solution, in 90-min recording sessions after 4h of water deprivation. The histograms of ILIs indicate that licking typically occurred at a preferred ILI of about 130-140ms with evidence of bimodal or multimodal distributions due to occasional licking failures. We found that the longer the pause between bursts of licks, the shorter was the first ILI of the burst. When bursts of licks were preceded by a pause >4 s, the ILI was the shortest (~110ms) at the beginning of the burst, and then it increased rapidly in the first few licks and slowly in subsequent licks. Interestingly, the first ILI of a burst of licks was not significantly different when licking any of the 3 solutions, but subsequent licks exhibited a temporal pattern characteristic of each solution. The rapid deceleration in intraburst licking rate was due to an increase from ~27ms to ~56ms in the tongue-spout contact duration while the intercontact interval was only slightly changed (80-90ms). Therefore, the contact duration seems to be the major factor that increases the variability in the ILIs and could be another means for the rat to adjust the amount of fluid ingested in each individual lick.

Distinct neural ensembles in the rat gustatory cortex encode salt and water tastes

The gustatory cortex (GC) is important for perceiving the intensity of tastants but it remains unclear as to how single neurons in the region carry out this function. Previous studies have shown that taste-evoked activity from single neurons in GC can be correlated or anticorrelated with tastant concentration, yet whether one or both neural responses signal intensity is poorly characterized because animals from these studies were not trained to report the intensity of the concentration that they tasted. To address this issue, we designed a two-alternative forced choice (2-AFC) task in which freely licking rats distinguished among concentrations of NaCl and recorded from ensembles of neurons in the GC. We identified three neural ensembles that rapidly (<300 ms or ∼2 licks) processed NaCl concentration. For two ensembles, their NaCl evoked activity was anticorrelated with NaCl concentration but could be further distinguished by their response to water; in one ensemble, water evoked the greatest response while in the other ensemble the lowest tested NaCl concentration evoked the greatest response. However, the concentration sensitive activity from each of these ensembles did not show a strong association with the behaviour of the rat in the 2-AFC task, suggesting a lesser role for signalling tastant intensity. Conversely, for a third neural ensemble, its neural activity was well correlated with increases in NaCl concentration, and this relationship best matched the intensity perceived by the rat. These results suggest that this neuronal ensemble in GC whose activity monotonically increases with concentration plays an important role in signalling the intensity of the taste of NaCl.

Genetic control of a central pattern generator: rhythmic oromotor movement in mice is controlled by a major locus near Atp1a2.

Fluid licking in mice is a rhythmic behavior that is controlled by a central pattern generator (CPG) located in a complex of brainstem nuclei. C57BL/6J (B6) and DBA/2J (D2) strains differ significantly in water-restricted licking, with a highly heritable difference in rates (h2≥0.62) and a corresponding 20% difference in interlick interval (mean ± SEM = 116.3±1 vs 95.4±1.1 ms). We systematically quantified motor output in these strains, their F1 hybrids, and a set of 64 BXD progeny strains. The mean primary interlick interval (MPI) varied continuously among progeny strains. We detected a significant quantitative trait locus (QTL) for a CPG controlling lick rate on Chr 1 (Lick1), and a suggestive locus on Chr 10 (Lick10). Linkage was verified by testing of B6.D2-1D congenic stock in which a segment of Chr 1 of the D2 strain was introgressed onto the B6 parent. The Lick1 interval on distal Chr 1 contains several strong candidate genes. One of these is a sodium/potassium pump subunit (Atp1a2) with widespread expression in astrocytes, as well as in a restricted population of neurons. Both this subunit and the entire Na+/K+-ATPase molecule have been implicated in rhythmogenesis for respiration and locomotion. Sequence variants in or near Apt1a2 strongly modulate expression of the cognate mRNA in multiple brain regions. This gene region has recently been sequenced exhaustively and we have cataloged over 300 non-coding and synonymous mutations segregating among BXD strains, one or more of which is likely to contribute to differences in central pattern generator tempo.

Multiple Processes Underlie Benzodiazepine-Mediated Increases in the Consumption of Accepted and Avoided Stimuli

Hyperphagia is a reported side effect of anxiolytic benzodiazepines such as chlordiazepoxide (CDP). Prior research has focused primarily on the ingestive responses to sweet or solid foods. We examined CDP effects on licking for normally accepted and avoided taste solutions across a range of concentrations. The effect of CDP (10 mg/kg) versus saline on the licking patterns of water-restricted rats for water and 3 concentrations of sucrose, saccharin, NaCl, monosodium glutamate (MSG), citric acid, and quinine (Q-HCl) solutions was evaluated during 1 h tests. CDP increased meal size for all tastants except citric acid. Analysis of licking microstructure revealed 3 dissociable effects of CDP. CDP affected oromotor coordination as indicated by a uniform increase in the modal interlick interval for all stimuli. CDP increased meal size as indicated by shorter pauses during consumption of water, MSG, and weaker saccharin concentrations, and by fewer long interlick intervals (250-2000 ms) for normally avoided tastants. CDP also increased meal size by increasing burst size, burst duration, and the initial rate of licking for most solutions, suggesting increased hedonic taste evaluation. CDP did not affect variables associated with postingestive feedback such as meal duration or number of bursts, and the results also suggest that CDP did not enhance the perceived taste intensity. We hypothesize that the reduction of pause duration is consistent with an increased motivation to sample the stimulus that synergizes with changes in taste-mediated responsiveness to some but not all stimuli to yield increases in the consumption of both normally accepted and avoided taste stimuli.

Not so fast: taste stimulus coding time in the rat revisited

Behavioral and electrophysiological studies suggest that rats can identify a taste stimulus with a single lick, in <200 ms. However, the conditions under which these conclusions were drawn varied widely across experiments. We designed a series of experiments to assess the effects of the number of licks of a tastant that are available, tastant concentration and prior learning experience on the speed with which a tastant can modify behavior. To accomplish this we tested exemplars of four basic taste qualities (quinine, 0.1 mM; NaCl, 100 mM; saccharin, 4 mM, or sucrose, 100 mM; citric acid, 10 mM) in rats that were conditioned to avoid quinine. Taste stimuli were available for one, two, or three licks on separate days. All tastants were presented in a randomized order interspersed with water rinse licks presented on a variable ratio schedule. A tastant-specific significant increase in the proportion of long pauses in licking following quinine presentation was defined as evidence of “behavioral identification.” Rats with aversion training given three licks of all taste stimuli paused significantly more often after quinine by the fourth interlick interval, ~580 ms. Control rats showed no evidence of quinine (0.1 mM) identification. When rats in all conditioning groups were tested with a high concentration of quinine (10 mM), a single lick was sufficient to produce significant pausing after quinine, but not until the fourth interlick interval, i.e., ~580 ms. Testing rats with only two tastants rather than four in a session had no effect on the speed of quinine identification. Present data confirm that a single lick is sufficient for rats to identify a taste stimulus, but that additional licks occur before evidence of identification is apparent. Furthermore, learning, tastant concentration and motivation to drink can all modify the speed of behavioral identification.

Feed efficiency, food choice, and food reward behaviors in young and old Fischer rats

Increased susceptibility to energy imbalance and anorexia in old age are risk factors for malnutrition during aging, but the underlying mechanisms are not well understood. Here, we explored changes in taste-guided hedonic value ("liking") and motivation to obtain ("wanting") palatable foods as potential mediators of age-associated anorexia and weight loss in old Fischer-344 rats. "Liking" as measured by the number of positive hedonic orofacial responses to sucrose and corn oil was not different in old compared with young rats. Taste-guided, low effort "wanting" as measured by the number of licks per 10 seconds was also not different, although old rats exhibited a slight oromotor impairment as revealed by significantly increased interlick intervals. Medium effort "wanting" as measured by performance in the incentive runway was significantly decreased in old versus young rats. Although decreased net running speed was partially accountable, significantly increased duration of distractions suggested additional deficits in motivation and/or reinforcement learning. Together with early satiation on corn oil but not sucrose in aged rats, these changes are likely to have resulted in the significantly greater sucrose preference of old rats in 12-hour tests, and may ultimately lead to reduced energy intake and weight loss.

Analysis of licking microstructure provides no evidence for a reduction in reward value following acute or sub-chronic phencyclidine administration

The N-methyl D-aspartate antagonist phencyclidine (PCP) is purported to mimic the negative, cognitive and positive symptoms of schizophrenia. Thus, acute and sub-chronic PCP treatment in rodents might produce anhedonia, a decrease in the pleasure produced by rewards. Experiment 1 investigated whether acute PCP treatment changes the value of sucrose. A comparison was made to (+)MK-801, a drug often used interchangeably with PCP in preclinical studies. Experiment 2 assessed the effects of withdrawal from sub-chronic PCP treatment on the value of sucrose. Experiment 1 examined the dose-response effects of PCP and (+)MK-801 on licking microstructure during sucrose consumption. Experiment 2 assessed the effects of withdrawal from sub-chronic PCP treatment (5 mg/kg twice daily for 7 days), on licking microstructure during sucrose consumption. Locomotor activity testing was carried out in experiment 2 to confirm the sensitisation effect of the PCP regimen on amphetamine-induced hyperlocomotion. Low to moderate acute doses of PCP and (+)MK-801 increased the amount of sucrose consumed. Higher doses decreased consumption and the number of licks per cluster (cluster size) but also increased the average inter-lick interval, which may indicate motor impairment. There was no evidence that withdrawal from sub-chronic PCP treatment produced decreases in consumption or lick cluster size. Following acute PCP treatment, we found no evidence of reduced reward value without the presence of confounding motor deficits. Sub-chronic PCP withdrawal also produced no decrease in reward value. Therefore, the current results indicate that neither acute PCP treatment nor sub-chronic PCP withdrawal produce consummatory anhedonia.

An analysis of licking microstructure in three strains of mice

Mouse models of feeding provide a useful tool for elucidating the molecular pathways of energy regulation. The majority of studies in mice have been limited to intake analyses conducted over extended periods of time, which fail to distinguish between a variety of factors that influence nutrient intake. Using licking microstructure analyses we examined both the size and number of licking bursts for water, polycose, sucrose and lecithin in three strains of mice (C57BL/6J, 129Sv/ImJ and C57129F1 hybrids), using pause criteria (250–500, >500 and >1000 ms) that have previously been described in the rat. Burst size and number varied both as a function of tastant concentration and mouse strain; however, these differences were most evident with the >1000 ms pause criterion. Consistent with previous reports, during water consumption C57 mice showed longer mean interlick intervals, a larger number of bursts but reduced burst size relative to the two other strains. F1 mice showed larger burst sizes for polycose, while C57 mice displayed a greater number of bursts for both polycose and sucrose. Both 129 and F1 mice were insensitive to sucrose concentration, whereas C57 mice showed attenuated lecithin intake influenced by a reduction in the size of bursts for this tastant. These results suggest that these strains of mice display differences in the pattern of licking that are most evident with the use of larger pause criteria. These differences in licking behavior might reflect influences of genetic background on pre- and post-ingestive factors controlling intake, the reinforcing properties of each tastant, or native differences in licking style.

Reduced palatability in lithium- and activity-based, but not in amphetamine-based, taste aversion learning.

Conditioned taste aversions (CTA) based on lithium chloride (Experiment 1), amphetamine (Experiment 2), and wheel running (Experiment 3) were examined using the analysis of the microstructure of licking to measure the palatability of the taste serving as the conditioned stimulus (CS). Pairing saccharin with amphetamine reduced saccharin intake without reducing the size of licking clusters, initial lick rate, or the distribution of inter-lick intervals (ILIs) within a cluster. By contrast, pairing saccharin with lithium or wheel-running reduced saccharin intake as well as lick cluster size, initial lick rate, and the distribution of ILIs within a cluster. As lick cluster size, initial lick rate, and ILI distribution can be used as indices of stimulus palatability, the current results indicate that taste aversions based on either lithium or activity reduced the palatability of the CS. This suggests that aversions based on both lithium and wheel running involve conditioned nausea to the CS taste. The absence of similar changes in licking microstructure with amphetamine-based CTA is consistent with other evidence indicating this does not involve nausea.

Effects of noxious stimulation of orofacial tissues on rat licking behaviour

Objective Since there is limited information of the effects of orofacial pain on oromotor behaviour, the aim of this study was to test the effects of injection of the algesic chemical glutamate into orofacial tissues on licking behaviour in rats. Design Male Sprague-Dawley rats were trained to carry out stereotyped licking from a water spout connected to a force transducer, and once they met preset licking motor requirements (peak force of licking of 2–20 g, interlick interval of 0.11–0.19 s), their masseter muscle or tongue was injected with either isotonic saline (0.9%, 5 μL) or glutamate (1.0 M, 5 μL) and several parameters of their licking performance were re-assessed. Results There were significant effects ( P < 0.05; 1-way repeated measures ANOVA) of glutamate injection into the tongue on the number of clusters of licks, the number of licks per cluster, the intercluster period, the peak force of licking and the interlick interval, but there were no significant ( P > 0.05) effects on licking of isotonic saline injection into the tongue or isotonic saline or glutamate injection into the masseter muscle. Conclusions These findings provide the first documentation that noxious stimulation of the tongue, but not of the masseter muscle, has a modulatory effect on licking behaviour in the rat and suggest that the neural substrate for licking may be sensitive to selective nociceptive inputs from the orofacial region.