Ethanol-induced grooming in mice selectively bred for differential sensitivity to ethanol

In rats, excessive grooming follows the application of several forms of stress. The injection of alcohol may be considered as a stressor, since it increases plasma corticosterone levels. The present study examines the effects of ethanol injections on grooming in two lines of mice selected for differences in their hypnotic response to ethanol, i.e., the long sleep (LS) and short sleep (SS) lines developed at the Institute for Behavior Genetics at the University of Colorado at Boulder. Various subhypnotic doses of ethanol produced excessive grooming in the SS line, but this did not occur in the LS line. The SS mice also displayed more "novelty-induced" grooming compared to the LS mice after repeated exposure to the testing situation. The increase in excessive grooming in both the ethanol-induced and the novelty-induced excessive grooming situations was most apparent in the second half of the observation period.     

Grooming and yawning trace adjustment to unfamiliar environments in laboratory Sprague-Dawley rats (Rattus norvegicus)

The authors studied grooming and yawning caused by mild stress in laboratory Sprague-Dawley rats (Rattus norvegicus). Two groups received 3 and 6 sequences of 5 foot shocks at random intervals (RI) and fixed intervals (FI), respectively. A 3rd group was not shocked (NS). The groups were exposed for 60 min twice. Grooming did not differ among groups, but yawning diminished with RI. Yawning increased and grooming decreased with the 2nd exposure, except in RI in which grooming increased. In NS and FI, grooming prevailed during the first 20 and 30 min, respectively, whereas yawning dominated the remainder of the time. In RI, grooming occurred more than yawning. An upward shift on this scale causes grooming to substitute yawning, whereas a downward shift causes the reverse effect.     

Increased novelty-induced grooming in aged rats: a preliminary observation

Age-related changes in grooming activity in female Fischer-344 rats were observed in a home cage and in a novel testing chamber for 50 min. Compared to the home cage condition with brief handling treatment, excessive grooming was found in the novel situation. The amount of novelty-induced grooming of aged rats (26-28 months) was about two times that of young animals (6-8 months). This increase in novelty-induced grooming of aged animals was attributable to an increase in the number of grooming bouts, prolongation of each grooming bout, and a slight increase in the duration of licking elements. However, there were no age differences in the percentage of face washing and the duration of face-washing elements. These results are discussed in terms of behavioral aging and age-related changes in peptidergic pathways in the brain.     

Opiates and homing

Beginning at 15 days of age. Long-Evans rat pups were trained to run toward their home cage in a T-maze task. Morphine (.5-1.0 mg/kg sc) slowed initial acquisition running times but did not change the number of trials required to learn the position habit. Morphine markedly impeded extinction of the homing behavior. Opiate-treated animals ran as accurately and as quickly toward home on the 12th day of extinction as on the first (10 trials given per day). Conversely, naloxone (1 mg/kg sc) reduced resistance to extinction. The morphine effect was not state-dependent since the drug also impeded extinction in animals that had acquired the task under saline. The morphine effect was blocked by naloxane, which indicates that the increased resistance to extinction was due to an opiate receptor effect. These results indicate that morphine has a strong capacity to sustain a social habit in the absence of reinforcement.     

MK-801与环境线索交互作用对吗啡行为敏感化的影响

为探讨MK-801与环境线索交互作用对吗啡诱导行为敏感化的影响,将42只大鼠随机分为对照组,MK-801组,吗啡组（匹配和非匹配）和MK-801+吗啡组（匹配和非匹配）。行为敏感化模型建立分为发展期,戒断期和表达期三个阶段。实验结果发现：同时给予MK-801（0.1mg·kg-1）会促进吗啡（5mg·kg-1）诱导大鼠行为敏感化的发展,而且会使MK-801成为大鼠行为敏感化表达所必需的条件性刺激。MK-801的内部线索作用过强,从而削弱了环境的外部线索作用。研究结果表明：MK-801对吗啡诱导行为敏感化的影响存在状态依赖（state-dependency）现象,提示在NMDA受体与行为敏感化关系的研究中应考虑选择刺激特性更小的药物     

Food-deprivation level alters the effects of morphine on pigeons'' key pecking.

Four pigeons pecked response keys under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food presentation. Components alternated separated by 15-s timeouts; each was presented six times. Pigeons were maintained at 70%, 85%, and greater than 90% of their free-feeding weights across experimental conditions. When response rates were stable, the effects of morphine (0.56 to 10.0 mg/kg) and saline were investigated. Morphine reduced response rates in a dose-dependent manner under the fixed-ratio schedule and at high doses under the fixed-interval schedule. In some cases, low doses of morphine increased rates under the fixed-interval schedule. When pigeons were less food deprived, reductions in pecking rates occurred at lower doses under both schedules for 3 of 4 birds compared to when they were more food deprived. When pigeons were more food deprived, low doses of morphine increased rates of pecking in the initial portions of fixed intervals by a greater magnitude. Thus, food-deprivation levels altered both the rate-decreasing and rate-increasing effects of morphine. These effects may share a common mechanism with increased locomotor activity produced by drugs and with increased drug self-administration under conditions of more severe food deprivation.     

Intracerebroventricular injection of anti-prolactin serum suppresses excessive grooming of pituitary homografted rats

Rats with endogenous hyperprolactinaemia, as induced by pituitary homografts under the kidney capsule, displayed increased grooming behavior as compared to that of sham-operated animals. Twelve days after surgery, intracerebroventricular injection of anti-prolactin serum (dilution 1:100, 1 microliter) suppressed the excessive grooming of homografted rats. These observations suggest that prolactin from a peripheral source may reach the central nervous system to affect brain mechanisms involved in grooming behavior.     

Effects of morphine, clonidine, and intensity change on electric-shock discrimination.

The effects of morphine, clonidine, and changes in stimulus intensity were examined in squirrel monkeys responding on one of two levers following brief presentations of one of two electric-shock intensities (0.1 and 0.5 mA). Responses were designated as correct or incorrect depending on which shock intensity had been presented and which lever was pressed. Morphine (0.42 to 1.80 mg/kg) and clonidine (0.075 to 0.18 mg/kg) decreased percentage correct responding. Morphine and clonidine also increased response latency and the number of shock presentations that were not followed by responses. Changes in shock intensity also decreased percentage correct responding but had no effect on response latency or on the number of shock presentations not followed by responses.     

Some fear-potentiating effects of fluprazine hydrochloride in mice

The fear-potentiating effects of fluprazine hydrochloride were explored in a series of five experiments. The drug was found to strongly inhibit entry into a novel open field, exploration of a complex maze, or approach to a novel object placed in the animal's home cage. Time sampling techniques were used to assess drug effects on frequencies of immobility, activity, and grooming and rearing responses prior to and for 70 min after footshock. There were no group differences during the 10 min immediately following shock but the groups diverged steadily in immobility, activity, and grooming for the remainder of the observations. Post-shock activity and grooming responses increased steadily towards baseline values among control mice but remained at low levels or declined among drug-treated mice. Immobility responses declined steadily among control mice but increased substantially among the fluprazine-treated mice throughout post-shock observations. Pairs of male mice treated with fluprazine were also found to maintain greater intermouse distances in a novel linear runway than pairs of undrugged adult males, juvenile males, or male-female pairs. It is suggested that fluprazine hydrochloride both potentiates fear and alters its time course in addition to interfering in some way with normal olfactory processes.     

Effects of morphine hydrochloride on social encounters between male mice

The effects of a single injection of morphine hydrochloride (0.3, 0.6, or 1.25 mg/kg) or physiological saline (0.9% NaCI) on the agonistic behaviour elicited by isolation in male mice were examined. Individually housed mice were exposed to anosmic “standard opponents” 30 minutes after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Morphine (at 0.6 and 1.25 mg/kg) significantly and dose-dependently decreased time spent in offensive (“threat” and “attack”) and “digging” behaviours but markedly increased “non-social exploration” without a significant increase of “immobility.” The lowest dose was completely ineffective in producing changes in any of the behaviours studied. It is concluded that these results present a specific ethopharmacological profile characterized by suppression of aggressive behaviour, increase in non-social explotation, and no evident impairment of motor activity. © 1993 Wiley-Liss, Inc.     

Long lasting increase in nociceptive threshold induced in mice by forced swimming: involvement of an endorphinergic mechanism

Mice submitted to forced swimming session(s) displayed a long lasting modification in their nociceptive threshold, assessed through their jump latency from a hot plate (55 degrees C). Thus two forced swimming sessions (6 min each, 8h apart), in water at 33 degrees C, increased by about 50% the jump latency when the hot plate test was performed 14 hours, 3 days or 6 days thereafter. The water temperature (16 degrees C vs 33 degrees C) had no critical influence in this respect. To be clearly effective (at 33 degrees C) the swimming session had to be performed twice (when performed only once it was irregularly effective); it apparently culminated for a 6 min duration, since its effectiveness was not significantly increased by extending the swimming time to 12 min or 18 min. Performing 2 forced swimming sessions (6 min each, 8h apart), 5 consecutive days, resulted in a suppression of the increase in jump latency in the hot plate test. The two forced swimming episodes-induced analgesia was prevented by the s.c. administration of diazepam (from 0.125 mg/kg) or morphine (from 5 mg/kg) or scopolamine (1 mg/kg) before each forced swimming episode. Morphine (7.5 mg/kg) was uneffective to prevent the induction of two forced swimming episodes-induced analgesia when it was administered immediately after each forced swimming session. Finally this analgesia was dose dependently reversed by naloxone (ID(50) = 0.14 mg/kg, s.c., 30 min before the hot plate test). It is hypothesized that the handling of mice immediately before the hot plate test induces the remembrance of the stress induced by previous forced swimming episodes, triggering a fear reaction which increases the nociceptive threshold.     

Antagonism of behavioral effects of bromocriptine by prolactin in female cats

The effects of the dopaminergic agonist bromocriptine (BC) and exogenously administered prolactin (PRL) on the spontaneous behavior of female cats were investigated. The objective was to test whether BC-induced behavioral effects may be antagonized by PRL. BC (6 mg/kg ip) administration induced abnormal behaviors such as limb flicks, abortive grooms, head/body shakes, and hallucinatory-like behavior/escape as well as excessive grooming. PRL (5 mg/kg ip) administration induced biphasic changes in grooming. The first change was an increase in grooming frequency averaging 256% of baseline control values and lasting for 1 h. This change was followed by reductions in grooming of 75 and 82.5% below baseline during Hours 2 and 3 postinjection, respectively. Combined BC and PRL treatment antagonized the frequency of BC-induced motor effects such as limb flicks, abortive grooms, and head/body shakes. Limb flicks occurred nine times more often 2 h after BC alone than after BC and PRL. The combined treatment also antagonized the excessive grooming observed after separate administrations of BC and PRL. The observed interactions between PRL and BC behavioral effects support the notion that PRL may be an important modulator of dopamine-dependent motor behavior in female cats.     

Conditioned nalorphine-induced abstinence changes: persistence in post morphine-dependent monkeys

Every tenth lever-press of three morphine-dependent rhesus monkeys was reinforced with food. A red light, initially a neutral stimulus, was presented every third or fourth session for 5 min before and 5 min after an intravenous injection of nalorphine, a morphine antagonist that produces an immediate abstinence syndrome in morphine-dependent monkeys. After several pairings, conditioned suppression of lever pressing, heart-rate decrease, vomiting, and excessive salivation were observed during the red-light period before nalorphine injection. No conditioned electrocardiogram, respiration or temperature changes occurred. After 10 red light-nalorphine pairings, morphine administration was completely discontinued and monkeys were then tested monthly for persistence of the conditioned responses. The red light paired with saline injection continued to suppress lever pressing and to produce heart-rate decreases after 60 to 120 days of complete abstinence from morphine. Subsequently, daily presentations of the red light-saline injection complex rapidly extinguished these conditioned responses. Nevertheless, they could be rapidly reinstated by additional nalorphine injections.     

Age- and sex-related induction of excessive grooming and "wet-dog" shakes by the codeinone RX 336-M in the rat

Peripheral administration of the dihydrocodeinone RX 336-M (6 mg/kg) stimulated vigorous "wet-dog" shakes and excessive grooming in young drug-naive rats. The effects of RX 336-M were greater in younger than in older animals of both sexes, and were greater in 39-day-old male rats than in female rats of the same age. In a second experiment, female rats were pretreated with testosterone benzoate (1 mg/kg/day) for 1 week prior to testing the effects of RX 336-M at 39 days of age. The sex hormone pretreatment enhanced the ability to RX 336-M to induce "wet-dog" shakes and excessive grooming in female rats. The results suggest that both sex- and hormone-dependent developmental status are critical in the display of the so-called "quasi-morphine withdrawal syndrome." The results imply, and are consistent with previous studies which suggest, that different neural mechanisms underlie the behavioral responses induced by ACTH and RX 336-M.     

Conditioned suppression by a stimulus associated with nalorphine in morphine-dependent monkeys

Three rhesus monkeys, physically dependent on morphine, were trained to press a lever for food on a fixed ratio of 10 responses. A tone, initially a neutral stimulus, was aperiodically presented every third or fourth session, 5 min before and after the intravenous injection of nalorphine, a morphine antagonist which produces an immediate withdrawal syndrome in morphine-dependent monkeys. After several sessions, conditioned suppression of food-lever response rate was observed. Conditioned bradycardia, emesis, and excessive salivation also occurred. In 40 to 45 sessions the conditioned suppression of food-lever response rate and the conditioned autonomic changes were extinguished by presenting pairings of a tone and saline injection. The monkeys were then reconditioned by presenting the tone aperiodically, every third or fourth session, 5 min before and after the intravenous injection of nalorphine. Results were similar to the initial conditioning sessions. Two rhesus monkeys not dependent on morphine were stabilized on a food schedule similar to that used for the first three monkeys. These monkeys showed no change in food-lever response rate during or after nalorphine injections.     

A method for determining the aversive threshold in the rat using repeated measures: Tests with morphine sulfate

The procedure described here provides an objective automated technique for the psychophysical assessment of the aversive threshold and allows the animal Ss to serve as their own controls. Sensitivity to drug effects, as well as comparisons between drugs, using the same animals are possible also. Using a rectangular tilt cage, the aversive threshold to grid shock was defined as that intensity avoided 75% of the time. Each shock intensity (30, 60, 90, 120, and 150 microA) was presented for 5 min on one side of the cage and then switched to the other side for 5 min, thereby forcing the animal to sample each shock intensity. Aversive thresholds were determined daily for each rat. The analgesic effects of morphine sulfate were compared to saline. Animals were tested for 3 days at each morphine dose level (2, 4, 8, and 16 mg/kg). Each 3-day morphine series alternated with 3 days of testing under saline. Significant differences were detected between saline and morphine at 4, 8, and 16 mg/kg.     

Initial environment influences amphetamine-induced stereotypy: subsequently environment change has little effect

Saline-treated and amphetamine-treated (7 mg/kg, ip, immediate) male rats from a Sprague-Dawley substrain were observed in two test environments designed to elicit different investigative responses in normal rats. Snout contact with the substrate was generated by placing the rat in a small enclosed cage. Absence of snout contact was induced by placement of the rat on a square elevated platform. Detailed ethological records were kept of locomotion, rearing, sitting, grooming, gnawing, and sleeping throughout the 90-min session. Amphetamine-treated rats incorporated environmentally contingent bodily postures into their forms of stereotyped behavior. The postures were characteristic of those evinced initially by the saline-treated rats in the same test environment. The control rats showed appropriate changes in their investigative behavior when the apparatus was changed at 10 and at 30 min postinjection. The amphetamine-treated rats, however, were completely unresponsive to such changes at 30 min and only partially so at 10 min postinjection. It was concluded that there is a temporal gradient of decreasing readiness to modify repetitive behavior after a single, large dose of amphetamine.     

Navigation in the Morris swim task as a baseline for drug discrimination: a demonstration with morphine

A morphine versus saline discrimination was demonstrated using the Morris swim task as the behavioral baseline. The apparatus was a large circular pool filled with water made opaque by floating polypropylene pellets. Rats were placed in the tank in randomly selected locations (12 trials per session) and could escape by swimming to a platform submerged 2 cm below the surface. Morphine (5.6 mg/kg) or saline was injected prior to training sessions. The position of the platform in a given session depended on the drug condition, thus forming the basis for discriminative responding. Three of the 4 rats acquired the discrimination, as evidenced by direct swims to the condition-appropriate platform. Generalization probe sessions were conducted following acquisition. Probe sessions were preceded by injections of morphine (0, 1.0, 3.0, 5.6, or 10.0 mg/kg) and involved placing the rat in the pool for 1 min without a platform. Swim patterns revealed a gradient, with probe swimming more concentrated in the area of the morphine platform position after higher morphine doses. In addition, dose-dependent increases in the likelihood of swimming first to the morphine-associated platform location were obtained. These results illustrate the generality of drug discrimination across different behavioral procedures, and of particular interest with respect to spatial learning, demonstrate interoceptive stimulus control of navigation.     

吗啡对不同距离条件下大鼠信号追踪和目标追踪的影响

条件刺激短暂呈现并消失后, 奖赏立即呈现, 多次匹配后诱导出动物对条件刺激(信号追踪)或奖赏呈现装置如食盒(目标追踪)的接近。条件刺激与食盒间的距离是影响信号/目标追踪反应和损害联结学习的重要变量, 成瘾药物能够增加奖赏的诱因动机, 进而增加个体的奖赏寻求行为。距离能否通过损害联结学习而减弱成瘾药物的动机放大作用尚未见到报道。本实验采用autoshaping模型, 考察8、30和60 cm距离条件下吗啡处理对大鼠信号追踪和目标追踪的影响。结果发现：(1)信号追踪随距离增加而减少, 目标追踪对距离不敏感。(2)急性吗啡处理减少8、30和60 cm条件下信号追踪而增加8和60 cm条件下目标追踪, 慢性吗啡处理在8和30 cm条件下减少信号追踪增加目标追踪; 消退检测中, 吗啡前暴露减少8和60 cm条件下信号追踪而增加60 cm条件下目标追踪。(3)辨别反转学习中, 吗啡前暴露使30和60 cm条件下的大鼠偏爱旧信号、辨别力受损, 减少8、30和60 cm条件下大鼠对新信号的接触。这些结果提示, 距离较少影响吗啡的信号追踪抑制作用和目标追踪增强效应, 而易化吗啡前暴露对反转学习的损害。说明距离是易化成瘾药物对联结学习不利影响而非反转其动机放大作用的重要因素。     

The effects of morphine on the production and discrimination of interresponse times

Recent experiments suggest that the effects of drugs of abuse on the discrimination of the passage of time may differ for experimenter-imposed and subject-produced events. The current experiment examined this suggestion by determining the effects of morphine on the discrimination of interresponse times (IRTs). Pigeons pecked a center key on a random-interval 20-s schedule of matching-to-sample trials. Once the interval had timed out, a choice trial randomly followed either a short (2- to 3-s) or long (6- to 9-s) IRT on the center key. Pecking the side key lit one color produced food after a short IRT, and pecking the side key lit the other color produced food after a long IRT. Two experimental phases differed in the functional role of the different key colors. Under control conditions, the IRT distributions had two modes, one at the lower bound of the short category and a smaller one at the lower bound of the long category. Pigeons accurately categorized the duration of the IRTs: One key color was pecked following short IRTs and the other key color was pecked following long IRTs. Morphine flattened the IRT distribution and reduced the accuracy of categorizing IRTs. Categorization of long IRTs was particularly disrupted. Morphine did not produce overestimation of time as assessed by the production or categorization of IRTs. These results are similar to those obtained previously for the effects of morphine on the discrimination of the duration of experimenter-imposed events.