Non-deprived Rats Research Articles

Social behavior, dominance, and social deprivation of rats determine drug choice

Relationships between social deprivation, dominance, and voluntary intake of ethanol (ETOH) and diazepam (D) were studied in male adult Wistar rats. Social behavior was registered by tetradic encounters in the open field prior to the rats' drug experiences. Social deprivation was induced by individual housing (LI) and contact caging (C). Nondeprived rats were housed in groups of four individuals (G) each. Social deprivation facilitated ETOH intake; LI rats consumed 30% more ETOH than G. Increase of deprivation by change of housing condition additionally raised ETOH consumption. ETOH experiences did not affect subsequet D choice. However, rats with a high ETOH consumption also preferred d. Individual drug disposition correlated with social dominance (in G: to social activity). Even in individual isolation dominant rats took less drugs than subordinate ones, but these rats raised their ETOH consumption when the housing conditions were changed. After nine months of voluntary ETOH intake and subsequently nine months without access to ETOH the rats showed signs of “behavioral dependence.” Compared to naive animals they took twice as much ETOH and even after adulterating ETOH by quinine a high preference was perpetuated. During this state modifying social factors were no longer effective.

Peripheral 5-carboxamidotryptamine (5-CT) elicits drinking by stimulating 5-HT 1-like serotonergic receptors in rats

Subcutaneous administration of the prototypical 5-HT 1-like agonist, 5-carboxamidotryptamine (5-CT), increased 2-h water intake by nondeprived rats (ED 50=0.04 μmol/kg). The 5-HT 1 agonists 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT, 0.04–0.32 μmol/kg) and RU 24969 (0.16 μmol/kg) did not produce drinking. The dipsogenic effect of 5-CT (0.08 μmol/kg) was prevented by the 5- HT 1 2 antagonist, methysergide (ID 50=4 μmol/kg), but not by 16 μmol/kg of the 5-HT 2 antagonist, ketanserin; the 5- HT 2 1 C antagonist, mianserin; or the 5-HT 3 antagonist, MDL 72222. 5-CT also increased drinking and reduced food intake when food-deprived rats were given 2-h access to mash. Methysergide (16 μmol/kg) inhibited both actions of 5-CT but an equimolar dose of the 5-HT 1/beta adrenergic antagonist, (−)-propranolol, blocked only the drinking. The 5- HT 2 1 C antagonist, ritanserin (16 μmol/kg), altered neither ingestive action of 5-CT although, by itself, ritanserin increased mash intake. The results suggest that activating a subtype of peripheral 5-HT 1-like receptor stimulates drinking in rats. This receptor is unlike either the 5-HT 1A or the 5-HT 1C sites found in the brain. Furthermore, the dipsogenic and anorectic actions of 5-CT occur independently.

Conditioned food preferences

Animals learn to prefer the flavors of foods on the basis of the foods’ postingestive nutritional consequences. This has been demonstrated with the conditioned flavor preference paradigm. With this paradigm, one flavor (the CS+) is paired with a nutrient that is orally consumed or is infused via a post-oral (e.g., intragastric) route; another flavor (CS-) is paired with a nonnutritive source. In subsequent two-choice tests, the rats displayed reliable preferences for the CS+ flavor over the CS- flavor. Very strong preferences (>95%) for sour or bitter flavors have been conditioned in nondeprived rats by pairing the CS+ with intragastric infusions of Polycose during 24-h/day training sessions. These conditioned preferences persisted for several weeks when the CS+ flavor was no longer paired with IG nutrient infusions. Thus, with the appropriate training procedures, conditioned flavor preferences can be as robust as conditioned flavor aversions.

Consummatory Contrast Effects in Nondeprived Rats Following Shifts in Sucrose Concentration

Successive positive and negative contrast effects in consummatory behavior were investigated following shifts in sucrose concentrations in nondeprived subjects. Forty-four male albino rats were given daily 5-min access to either a 4%- or 32%-sucrose solution across a 14-day preshift period. Subjects in each group were then assigned to either a control or shifted condition. Shifted groups were upshifted (4–32%) or downshifted (32–4%) for a 10-day postshift period. Negative contrast was apparent in both lick rate and time spent at the drinking tube across the first 4 days of postshift. Positive contrast effects were not obtained, but rather a significant effect opposite to positive contrast occurred. The improbability of the ceiling effect explanation for the present results is discussed. Differences relative to deprivation state and the role of perceptual (taste) factors in contrast effects are also examined.

Intra-midbrain raphe injections of the neurokinin-3 agonist senktide inhibit food and water intake in the rat

Microinjection and lesion studies have implicated the midbrain dorsal (DR) and median raphe (MR) nuclei in behavioral arousal. This behavioral state is manifested as locomotor hyperactivity, hyperphagia, hyperdipsia and increases in plasma corticosteroid release. Intra-midbrain raphe injections of the GABA A agonist muscimol elicit this behavioral activation. We have demonstrated that similar infusions of tachykinins produce locomotor hyperactivity through activation of neurokinin-3 (NK-3) receptors located on serotonin cell bodies. The purpose of the present study was to determine the effects of intra-MR and DR infusions of senktide, an NK-3 agonist, on food and water consumption in nondeprived rats. Male Sprague-Dawley rats were implanted with indwelling intra-MR or intra-DR cannula. Infusions of muscimol (25 ng/0.5 μl) into the MR increased water intake, while MR and DR infusions increased food consumption. In contrast, intra-MR injections of senktide decreased water intake and intra-MR and DR injections decreased food intake. The results suggest that the behavioral states induced by muscimol and neurokinin infusions into the raphe are distinct and that raphe/neurokinin pathways are involved in consummatory mechanisms.

Fat appetite in rats: The response of infant and adult rats to nutritive and non-nutritive oil emulsions

Fat appetite was studied in rats using corn oil and mineral oil emulsions. In Experiment 1 ingestive responses to intraoral infusions were measured in rat pups 6–15 days of age. By 12–15 days of age pups responded more to oil emulsions (10% and 30%) than they did to water or emulsifier solution. The corn and mineral oil emulsions were almost as effective as milk but less effective than sucrose (0.3 m) in stimulating ingestion. Experiments 2 and 3 examined the acceptance and preference for oil emulsions in adult rats. The corn oil and mineral oil emulsions were equally acceptable to non-deprived rats, as measured by 3-min and 30-min one-bottle tests. Food deprivation increased the one-bottle intake of both emulsions. In two-bottle tests, rats displayed a slight corn oil preference when non-deprived, but developed a strong preference when food deprived. Taken together, the results suggest that rats have an unlearned attraction to the orosensory qualities of emulsified oils and they learn to prefer corn oil based on its postingestive nutritive effects.

Corn oil and mineral oil stimulate sham feeding in rats

To determine the orosensory effects of oils on ingestion, we measured the 1-bottle intake of corn oil and of mineral oil during 30 minutes of sham feeding in rats that were food deprived overnight or nondeprived. Rats sham fed both oils. Food-deprived rats ingested significantly more of both oils than nondeprived rats. Rats discriminated corn oil from mineral oil and as little as 0.78% corn oil emulsion from water. When rats sham fed 8 dilutions of corn oil, intake was an inverted-U function of concentration with maximal intakes produced by 12.5%, 25% and 50% corn oil emulsions. Despite similar, sometimes equal, intakes of corn oil and mineral oil in 1-bottle tests, food-deprived and nondeprived rats showed a strong preference for corn oil in 2-bottle, sham-feeding, preference tests. The sensory mechanisms that mediate the oral effects of oil on intake and preference are not known, but the olfactory and trigeminal sensory systems are the most likely candidates. Further work is required to characterize the potency, sensitivity, and discriminability of the orosensory effects of oils, the mechanisms that mediate them, and their role in the control of fat intake.

Opioid effects on intake of sweet solutions depend both on prior drug experience and on prior ingestive experience

Two experiments investigated the effect of opioids on ingestion of sweet solutions in non-deprived rats. Experiment 1 replicated previous work from our laboratory showing virtually complete inhibition of sucrose and saccharin intake during 10 days of daily naloxone treatment. During recovery, prior naloxone experience significantly stimulated sucrose intake but had no effect on saccharin intake. In the absence of naloxone treatment, ingestive experience alone reduced naloxone's typical intake-suppressant effect. These findings suggest that drug experience and ingestive experience may interact to determine the intake-suppressant effect of naloxone. Experiment 2 examined the effects of opioid agonists on sucrose ingestion during 10 days of initial drug treatment and 5 days of recovery. A low dose of the kappa agonist U-50,488H significantly stimulated sucrose ingestion during the drug treatment period and this effect persisted for several days after treatment ended. Initial (non-significant) intake suppressant effects of the mu agonist morphine or a high dose of U-50,488H tended to decrease with repeated testing and did not reappear during recovery. These data suggest that in addition to immediate, direct effects on motivation, opioids may affect long-term changes in responsiveness to sweet tastes.

Effect of fourth ventricular neuropeptide Y and peptide YY on ingestive and other behaviors

We studied the effect of fourth intracerebroventricular administration of neuropeptide Y (NPY) and peptide YY (PYY) on ingestive and other behaviors in awake nondeprived rats. Injection of NPY or PYY into the fourth ventricle produced a significant dose-related increase in food intake and reduction in the latency to eat. PYY was more potent than NPY in increasing food intake and decreasing latency to eat, suggesting that PYY-preferring receptors sensitive to the orexigenic effects of NPY and PYY exist in the hindbrain. In addition, both peptides increased water intake when food was present but not when food was absent, suggesting that a neural substrate supporting a direct action of NPY and PYY on water intake is not present in the hindbrain. In time sampling of behaviors occurring during a 90-min feeding test, we found that both peptides increased the time spent eating and reduced grooming. In addition PYY, but not NPY, reduced apparent sleep and increased exploratory activity. This suggests that PYY, but not NPY, influences a hindbrain neural substrate involved in sleep and activity.

Winning isn't everything: Rats need only food deprivation and not food reward to efficiently traverse a radial arm maze

The present study examined the assumption that immediate food reward is the critical determinant of efficient performance on the radial maze. Food-deprived and nondeprived rats were run on a large-platformed, 8-arm radial maze that was either baited or unbaited. Food-deprived rats that were rewarded entered significantly more novel arms in their first eight choices than expected by chance, consistently ran to the ends of chosen arms, and increasingly chose adjacent arms over trials. Food-deprived rats that were unrewarded behaved in much the same way. In contrast, rats that were nondeprived and unrewarded did not choose novel arms at above chance levels, infrequently ran to the ends of chosen arms, and did not develop a consistent response strategy. Explanations of the development of organized behavior based on reinforcement, win-shift tendencies, or spontaneous alternation do not account for these results. Rats appear to have foraging strategies based on preorganized stimulus sensitivities and response dispositions that are readily engaged by food deprivation and result in efficient traversal of a radial maze even in the absence of food reward.

SCH 23390-Induced hypophagia is blocked by the selective CCK-A receptor antagonist devazepide, but not by the CCK-B/gastrin receptor antagonist L-365,260

The selective dopamine D-1 receptor antagonist SCH 23390 (30 μg/kg, SC) significantly reduced palatable food consumption by nondeprived rats in a 30-min test period. Prior administration of the selective CCK-A receptor antagonist devazepide (MK 329; L-364,718) blocked the hypophagic effect of SCH 23390. In contrast, prior administration of the selective CCK-B/gastrin receptor antagonist L-365,260 had no effect. Devazepide did not antagonize a matched hypophagic effect produced by the dopamine D-2 receptor antagonist raclopride (0.1 mg/kg, SC). These data direct attention to possible dopamine-cholecystokinin interactions in relation to the control of ingestional responses, and, more specifically, indicate possible functional relationships between D-1 and CCK-A receptor mechanisms.

Effects of a selective mu opioid receptor agonist and naloxone on the intake of sodium chloride solutions

Endogenous opioid peptides are thought to play a role in mediating the palatability or rewarding aspects of sweet tastes. There is also evidence, however, which suggests that opioids may influence the preference for the taste of salt as well. In the present studies, we measured the effects of central administration of naloxone and the mu agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) on the ingestion of salt solutions. In non-deprived rats given a choice of water and 0.6% saline, ICV injections of DAGO (1 and 3 nmol) significantly increased the intake of 0.6% saline; baseline water intake was minimal and was unaffected by DAGO. When rats were given a choice between water and 1.7% saline, DAGO stimulated both water and saline intake. Because 1.7% saline is a hypertonic solution, the increase in water intake may have been secondary to saline intake. In rats on a deprivation schedule in which water and 0.6% saline were available for only 2-3 h/day, there was a tendency for DAGO to increase 0.6% saline intake and decrease water intake, though these effects were not significant. In rats given water and 1.7% saline, DAGO increased saline intake and had no effect on water intake. Naloxone was also tested in water-deprived rats. Naloxone (20 and 50 micrograms) significantly decreased 0.6% saline intake; baseline water intake was low (3-5 ml) and was unaffected by naloxone. When rats were given a choice between water and 1.7% saline, naloxone (50 micrograms) significantly reduced water intake, while intake of 1.7% saline was slightly increased. These results suggest a role for central mu opioid receptors in mediating the preference for salt solutions.

Effects of preferential delta and kappa opioid receptor agonists on the intake of hypotonic saline

A previous study has implicated central mu opioid receptors in the preference for salt solutions. Because mu, kappa and delta receptors are all thought to play a role in food intake and/or the mediation of palatability, we performed a series of experiments to determine whether preferential agonists at kappa and delta receptors might also stimulate the intake of salt solutions. When injected centrally into nondeprived rats, two selective agonists at delta receptors caused increases in the intake of 0.6% saline; the intake of concurrently available water was either unchanged or slightly increased. The selective kappa agonist U-50, 488H had no effect on water or saline intake, whereas the preferential kappa agonist DAFPHEDYN caused a delayed increase in saline intake. These results indicate a role for central delta receptors in the preference for salt solutions, and are consistent with the suggestion that opioids play a role in the mediation of palatability.

The anorectic effect of SK&F 38393, a selective dopamine D1 receptor agonist: a microstructural analysis of feeding and related behaviour

An observational study was undertaken to provide a microstructural analysis of the effects of the selective dopamine D1 receptor agonist, SK&F 38393, on feeding and associated behaviours in the rat. Adult, male non-deprived rats were adapted to eating a meal of sweetened mash in a 30-min period. SK&F 38393 (3.0 and 10 mg/kg, SC) significantly reduced food consumption). It also reduced the frequency of feeding bouts and the local rate of eating, while there was an increase, at 10 mg/kg, in the mean duration of individual feeding episodes. The D1 receptor agonist also reduced the total duration of locomotor activity, but did not affect the total duration of rearing, grooming, sniffing, oral behaviours (other than feeding), or resting. The frequency of bouts of locomotion, rearing, grooming, and sniffing were reduced by SK&F 38393. Consideration of the time-courses for the several responses suggested that SK&F 38393 did not materially affect the form and sequence of behavioural responses in the test, although some changes occurred.

Reversal of the anorectic effect of (+)‐fenfluramine in the rat by the selective cholecystokinin receptor antagonist MK‐329

1. Experiments were conducted to determine whether or not the effect of (+)-fenfluramine (3.0 mg kg-1, i.p.) on food intake can be antagonized by the selective cholecystokinin receptor antagonist MK-239 (formerly L364,718; (3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1-H-1,4-benzodiazepin++ +-3-yl)-1H- indole-2-carboxamide). Two feeding paradigms were employed. In the first, non-deprived rats were familiarized with eating a highly palatable, sweetened mash in a 30 min test. In the second, freely-feeding rats were trained to consume powdered chow in their home-cages, and their intake was monitored over the first 6 h of the night-period. 2. In doses of 30.0 and 100.0 micrograms kg-1, s.c., MK-329 almost completely blocked the anorectic effect of (+)-fenfluramine in the palatable food intake test. These doses of MK-329 have previously been reported to antagonize the anorectic effect produced by exogenous cholecystokinin-octapeptide (CCK8) in rats. Both doses of MK-329 were also effective in significantly attenuating the anorectic effect of (+)-fenfluramine in nocturnal free-feeding animals over a 6 h-period. 3. MK-329 (10.0-100.0 micrograms kg-1, s.c.) failed to antagonize the anorectic effect of either the specific dopamine D2-receptor agonist quinpirole (0.3 mg kg-1, s.c.) or the beta-carboline FG 7142 (10.0 mg kg-1, i.p.) in the palatable food intake test. 4. MK-329 (10.0-300.Opgkg-1, s.c.) had no effect, when administered alone, on the level of palatable food intake in non-deprived rats, even when substantial satiation was produced by a pre-feeding procedure. Furthermore, MK-329 had no effect, when administered alone, on nocturnal food intake in freelyfeeding rats. 5. In conclusion, not only was MK-329 a potent antagonist of the effect of CCK8 on food intake, it also blocked the effect of (+)-fenfluramine to a significant degree. The effect of MK-329 was selective in that the anorectic effects of either quinpirole or FG 7142 remained unaffected. Administered alone, MK-329 did not affect food intake, indicating that its reversal of (+ -fenfluramine-induced anorexia was not secondary to an intrinsic hyperphagic effect. The results provide some evidence that the depressant effect of (+ )-fenfluramine on food intake depends on the activity of endogenous CCK.

Fluoxetine reduces food intake by a cholecystokinin-independent mechanism

The selective serotonin uptake inhibitor, fluoxetine (3.0–10 mg/kg), produced a significant dose-related suppression of palatable food consumption in nondeprived rats. The anorectic effect of fluoxetine (10 mg/kg) was not reversed by the potent and highly selective cholecystokinin receptor antagonist MK-329 [1-methyl-3-(2-indolyl) amino-5-phenyl-3H-1,4-benzodizepin-2-one], administered in doses of 10–100 μg/kg. Fluoxetine (10 mg/kg) also significantly reduced the consumption of powdered laboratory chow in a 6-hr nocturnal free-feeding test. The anorectic effect in this paradigm was also not antagonized by MK-329. In contrast to previous data for d-fenfluramine (which enhances serotonin release), these results indicate that fluoxetine may suppress food intake by a mechanism which is independent of endogenous cholecystokinin.

Tetradic Encounters of Wistar Rats (Rattus Norvegicus) After Social Deprivation: Individual Behavioural Features

In young but adult male Wistar rats the individual behavioural interactions during tetradic encounters in the open field were studied after three weeks of differential housing. The purpose was to look for social roles within the tetrade an to investigate the influence of social deprivation on interindividual differentiation. Behavioural features of each individual were established according to the time budget of the behaviour, locomotor and spatial parameters, and the recipience of social interactions by the other members of the tetrade. The most ralible feature during repeated encounters was social recipience which revealed significant positive inter-session correlations in group housed (G), contact housed (C), and individually housed (LI) rats. Among the housing groups the highest level of inter-session correspondence concerning nearly all the features was found in C individuals. The existence of social roles was suggested by interfeature correlation analyses. Clusters of significantly correlating features were detected which revealed both correspondences and differences between the housing groups. Each social role was characterized by a particular cluster; three of such roles were established: social activity, social attractivity, and exploration of the environment. The latter cluster and its attributed role was only present in non-deprived rats (G). Social activity was characterized by high levels of play and social investigation, and proximity to conspecifics whereas social attractivity was expressed by social recipience positively correlating to the performance of aggression and aggressive play. In LI individuals a discrimination between attractive and non-attractive animals developed some three minutes after the start of the encounter. Socially active rats preferred the proximity of attractive ones and tended to perform the same type of behaviour which the attractive one had shown during the last 30 seconds. C rats behaved in a similar way but a moderate inter-individual differentiation was detected already during the first minutes. In G role-specific differences were poorly expressed. In particular the behaviour of the active rat was less directed and related to the attractive animal. It is discussed to what extent social dominance expressing itself in playful interactions and social attractivity rather than in agonistic fight may be characteristic for establishing groups with an increasing degree of individual recognition.

Blockade of 8-OH-DPAT-induced feeding by dopamine antagonists

Feeding elicited by the 5HT1A agonist 8-OH-DPAT was blocked by pretreatment with the DA antagonists SCH-23390 and sulpiride, in two experiments conducted in non-deprived rats and in three experiments conducted after 4 h food deprivation. In deprived animals, 8-OH-DPAT prolonged the initial period of feeding. However, in non-deprived animals, 8-OH-DPAT delayed the onset of eating, and suppressed post-prandial resting; both SCH-23390 and sulpiride restored the normal pattern of behaviour. All three drugs suppressed grooming. The results suggest that 8-OH-DPAT elicits feeding by a secondary disinhibition of activity postsynaptic to DA neurons. The consequences of this mechanism for the interpretation of 8-OH-DPAT-induced feeding are discussed.

The selective dopamine D 1 receptor agonist SK&F 38393: Its effects on palatability- and deprivation-induced feeding, and operant responding for food

A series of experiments investigated the involvement of the dopamine D 1 receptor subtype in relation to feeding responses. The selective D 1 agonists, SK&F 38393 (1.0–20 mg/kg) and SK&F 75760 (5 mg/kg), significantly reduced palatable food consumption in nondeprived rats. The anorectic effect of SK&F 38393 (10 mg/kg) was additive with that of the selective D 2 receptor agonist, N-0437 (0.3 mg/kg). In nondeprived mice, SK&F 38393 had a stereoselective effect to reduce palatable food intake. At a peripherally-selective dose (3.0 mg/kg), the peripheral dopamine D 1 receptor agonist, fenoldopam, had no effect on food intake. At 10 mg/kg, however, it exhibited anorectic properties, although this may have been due to some penetration of the blood-brain barrier. In rats adapted to a food-deprivation schedule, SK&F 38393 (3.0–30 mg/kg) produced significant dose-dependent reductions in consumption of powdered chow and in lever-pressing for food pellets on a FR8 schedule of reinforcement. In rats adapted to a water-deprivation schedule, SK&F 38393 (3.0–30 mg/kg) was substantially less effective in reducing water intake. The results are discussed in terms of a possible selective effect of D 1 agonist activity on feeding behaviour.

Centrally administered opioid peptides stimulate saccharin intake in nondeprived rats

Endogenous opioid peptides are thought to play a role in mediating the pleasurable or rewarding aspects of the ingestion of certain foods and liquids. We therefore measured the effects of central administration of selective opioid agonists and naloxone on the intake of two concentrations of saccharin solution. All tests were performed on nondeprived rats, such that the taste of the solutions provided the primary incentive to consume. Intracerebroventricular (ICV) administration of the selective mu agonist [D-Ala 2,MePhe 4,Gly-ol 5]enkephalin (DAGO) and the selective delta agonist Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) (3 nmol) increased intake of a 0.15% saccharin solution by approximately 10 ml over 3 hr. Water was available simultaneously, but intake was minimal. The selective kappa agonist U-50,488H did not increase intake of the saccharin solution. Naloxone (30 and 100 μg, ICV) caused a 44% reduction in saccharin solution intake in the first hour; two- and three-hour cumulative intakes were not different from control. DAGO and DTLET were also tested when rats were given a weaker saccharin solution (0.006%) along with water. Both agonists caused small increases in saccharin and water intake, but the increases above baseline were much smaller than those observed with the more palatable 0.15% saccharin solution. These results are consistent with reports by others which suggest that endogenous opioids influence taste preferences or palatability. Further, they indicate a role for central mu and delta opioid receptors in the mediation of this influence.