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1.
The Fawn-Hooded rat (FH) strain has attracted the attention of some psychopharmacologists because of reports of its exaggerated immobility in the swim test, hypercortisolemia, excessive voluntary intake of alcohol, platelet and central serotonin abnormalities and subsensitivity to serotonergic agonists. However, there appears to be some controversy over several behavioral and physiological characteristics of these rats. The present paper proposes that the lack of reproducible findings can be traced to there being several distinct inbred strains of FH rats. Of the two compared in this communication, the FH/Wjd strain is more immobile in the forced swim test, spends more time in the open arms of the elevated plus maze, and drinks more saccharin and alcohol voluntarily than the FH/Har (Iowa Reactive) strain. Future workers are cautioned to report the source of their FH rats.  相似文献   

2.
The pyrazoloquinoline CGS 8216 (2-phenylpyrazolo-[4,3-c]-quinolin-3 (5H)-one, 0.05-2 mg/kg) and the beta-carboline ZK 93426 (ethyl-5-isopropyl-4-methyl-beta-carboline-3-carboxylate, 1-10 mg/kg) benzodiazepine receptor antagonists were evaluated for their capacity to modulate the behavioral actions of ethanol in alcohol preferring and -nonpreferring rats. When alcohol-preferring rats were presented with a two-bottle choice test between ethanol (10% v/v) and a saccharin (0.0125% g/v) solution, both antagonists dose-dependently reduced intake of ethanol by 35-92% of control levels on day 1 at the initial 15 min interval of the 4 h limited access. Saccharin drinking was suppressed only with the highest doses. CGS 8216 (0.25 mg/kg) and ZK 93426 (4 mg/kg) unmasked the anxiolytic effects of a hypnotic ethanol dose (1.5 g/kg ethanol) on the plus maze test in alcohol-preferring rats, but potentiated the ethanol-induced suppression in alcohol-nonpreferring rats. CGS 8216 (0.25 mg/kg) and ZK 93426 (4 mg/kg) attenuated the ethanol (0.5 and 1.5 g/kg)-induced suppression in the open field in alcohol-nonpreferring rats; however, CGS 8216 potentiated the depressant effects of the lower ethanol dose (0.5 g/kg) in alcohol-preferring rats. These findings provide evidence that benzodiazepine receptor antagonists may differentially modulate the behavioral actions of ethanol in alcohol-preferring and-nonpreferring rats. It is possible that the qualitative pharmacodynamic differences seen in the present study may be related to selective breeding for alcohol preference. The findings indicate the potential for development of receptor specific ligands devoid of toxic effects which may be useful in the treatment of alcohol abuse and alcoholism.  相似文献   

3.
To further understand the relationship between emotional state and alcohol intake in rats, the tendency to emit ultrasonic vocalizations in response to an aversive, but nonpainful, air puff stimulus was tested in several rat lines. Included in this group were Maudsley Reactive (MR) and Non-Reactive (MNR) rats, and several lines of rats with either high ethanol preference or a low ethanol preference: Preferring, (P), Alko-Alcohol (AA), and Fawn-Hooded (FH) animals; and Non-Preferring (NP), Alko-Non-Alcohol (ANA), and Flinders Resistant Line (FRL). MR rats emitted fewer ultrasonic vocalizations (USVs) and showed less preference for ethanol than did MNR animals. An overall analysis that included the P, NP, FH, FRL, AA, and ANA groups demonstrated a significant negative correlation between the total number of USVs emitted and ethanol consumption. NP, FRL, and especially ANA rats (low ethanol-preferring) emitted the most USVs--to an extent similar to that typically found for normal rats. The duration of vocalizing was higher only in the NP and the FRL rats the relative to their P and FH comparison groups, respectively. In the ethanol-preferring and nonpreferring lines, the numbers of USVs emitted correlated positively with the duration of vocalizing, but not with the latency to vocalize, which in turn did not correlate strongly with ethanol intake. The latency to vocalize did not correlate significantly with ethanol intake across all drinking lines or MR or MNR rats, but was found to be higher in FH and AA rats relative to their nondrinking comparison groups. These associations suggest that the relationship between emotional state and ethanol drinking is complex and cannot be attributed to a simple elevated state of anxiety or emotionality. Further examination of the central nervous system mechanisms mediating the difference in USVs between paired lines of ethanol-preferring and nonpreferring rats may identify neurochemical factors that predict ethanol preference.  相似文献   

4.
We previously reported that single administration of ibogaine, an indol alkaloid with antiaddictive properties, dose dependently reduced alcohol intake in three strains of alcohol-preferring rats. The present study examined the effect of different doses of a newly developed nontoxic ibogaine analogue, 18-methoxycoronaridine (18-MC), on alcohol intake. Selectively bred alcohol-preferring rats received a single intraperitoneal injection of vehicle or 5, 20 and 40 mg/kg of 18-MC at 9:30 AM, and their consumption of alcohol, water and food was measured for 24 h. Our results demonstrate that a single injection of 18-MC significantly and dose dependently attenuated alcohol consumption and preference and commensurately increased water intake. Only the highest dose of 18-MC significantly decreased food intake. Although the true mechanism of action of 18-MC in suppressing alcohol intake is not yet fully understood, it may, like ibogaine, exert its attenuating effects on alcohol consumption by modulating neurotransmitters believed to be involved in the regulation of alcohol intake.  相似文献   

5.
Injections in the nucleus basalis magnocellularis (NBM) of the tachykinin (TK) NK-3 receptor agonist [Asp5,6,MePhe8]substance P(5-11), also referred to as amino-senktide (NH2-SENK), markedly reduced alcohol intake in genetically selected alcohol-preferring rats, offered 10% ethanol 2 h/day. The threshold dose in the NBM was 0.5 ng/site, while neither 1 nor 10 ng/rat of NH2-SENK inhibited alcohol intake following administration into the lateral ventricle. Injection of NH2-SENK, 25 ng/site, in the NBM did not modify water or food intake in water deprived rats, providing evidence for the behavioral selectivity of the effect on ethanol intake. The selective TK NK-3 receptor antagonist, R-820, injected in the NBM at the dose of 1000 ng/site 5 min before NH2-SENK 5 ng/site, significantly reduced the effect of NH2-SENK. The selective TK NK-1 receptor agonist [Sar9,Met(O2)11]substance P inhibited alcohol intake following injection in the NBM only at 25 ng/site; but the same dose induced marked grooming and inhibited also water intake in water deprived rats. The present results confirm that TK NK-3, but not NK-1, receptor agonists selectively inhibit ethanol intake in alcohol-preferring rats and suggest that the NBM is a site of action for their effect.  相似文献   

6.
Previous studies showed that the 5-HT2 receptor antagonist, amperozide, is somewhat more potent than the opiate antagonist, naltrexone, in reducing alcohol drinking in high alcohol-preferring (P) rats. The purpose of this study was to determine in the P rat whether the effect of either drug could be due, in part, to an alteration in gustatory function. In an unlimited, 24-h free choice paradigm, P rats were offered water simultaneously with either a highly palatable 0.1% saccharin solution or a 1:4 dilution of Nestlé Sweet Success chocolate drink. Throughout all phases of the study, the P rats always consumed significantly greater volumes of the chocolate drink than of the saccharin solution, i.e., 526 ml/kg vs. 181 ml/kg, respectively. Successive 12-day experimental periods consisted of three phases: a 4-day predrug control interval; 4 days of administration of saline control vehicle or either drug; and a final 4 day postdrug interval. In a counterbalance design, saline, amperozide (1.0 or 5.0 mg/kg) or naltrexone (2.5 or 5.0 mg/kg) was administered subcutaneously twice daily at 1600 and 2200 h for 4 days. Amperozide and naltrexone significantly reduced the drinking of chocolate in a dose-dependent manner. Conversely, only the two higher doses of amperozide and naltrexone decreased the intake of saccharin significantly. Thus, these findings suggest that different populations of central serotonin and opioid receptors concurrently underpin, in part, the preferences for both palatable and/or nutrient fluids. Finally, because both the opiate and 5-HT2A antagonists reduce the ingestion of saccharin and chocolate solutions differentially, it is apparent that preferences for alternative palatable fluids should be examined when candidate drugs are screened for suppressing alcohol drinking and ultimately the treatment of alcohol abuse.  相似文献   

7.
Although isolated rat pups emit ultrasonic vocalizations (USVs), those kept warm and undisturbed in the home cage with their littermates seldom do. Drugs were administered to 10-day-old Wistar rat pups in the home cage to determine whether pharmacological agents can elicit USVs in this familiar environment. Ss were injected with U50,488, a highly selective kappa opioid agonist; pentylenetetrazol (PTZ), an anxiogenic drug that binds at the GABA-benzodiazepine receptor complex; or naltrexone (NLX), an opiate receptor blocker, and then were returned to their littermates in the home cage. U50,488 increased USV and activity levels, lowered body temperature, and disrupted contact with littermates. PTZ raised activity levels but had a smaller effect on vocalization rates and did not alter temperature or contact with littermates. Behavioral measures and body temperature were unchanged by NLX. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

8.
Although numerous biochemical and physiological differences have been shown to be correlated with alcohol preference, less is known about behavioral factors that may correlate with alcohol preference. Using a signaled barpressing task, alcohol-preferring (P; n = 18) and alcohol-nonpreferring (NP; n = 19) rats were compared for their ability to learn an appetitive and an aversive task. Results showed that P rats had difficulty learning the tasks in comparison with NP and nonselected, control rats when appetitive training was given first. However, if aversive training came first, the NP rats performed poorly in comparison with the P and nonselected rats. These results suggest that these lines of rats may differ in behavioral inhibition and sensitivity to conditioned fear. Furthermore, these behavioral differences may offer a richer analysis of the traits that were co-selected with the alcohol-seeking and alcohol-avoiding phenotypes.  相似文献   

9.
C. P. Richter and K. H. Campbell (1940b) originally defined taste threshold as "the point at which the rats first indicated that they recognized a difference between the distilled water and the solutions" (p. 34). The present study sought to apply this simple behavioral measure to the investigation of strain differences in taste sensitivities, particularly with respect to predictive relationships in ethanol, saccharin, and quinine preference. Fawn-Hooded, Lewis, and Wistar rats were presented with gradual increments in concentration of ethanol (0.01-15%; C. P. Richter & K. H. Campbell, 1940a), saccharin (0.002-3%) or quinine (0.000 1-0.0055). Results showed that although intake for saccharin was similar in all strains, consumption of ethanol and quinine differed among the groups. Although previous research has proposed that sweet preference is a promising behavioral marker for ethanol preference, these results suggested that bitter preference may be a more reliable predictor of ethanol preference in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

10.
The present study investigated the effects of the cannabinoid receptor agonist CP 55,940 (1-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) and the cannabinoid receptor antagonist SR 141716A (N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1 H-pyrazole-3-carboxamide hydrochloride) on ultrasonic vocalizations, body temperature and activity in 11-13-day-old rat pups. Testing occurred in a 5-min session 30 min following drug administration. CP 55,940 produced a dose-dependent decrease in ultrasonic vocalizations, with a 1000-micrograms/kg dose causing an almost complete inhibition of calls. Doses of 100 and 1000 micrograms/kg of CP 55,940, but not 10 micrograms/kg, caused significant hypothermia in the pups and the 1000 micrograms/kg dose also inhibited activity. The cannabinoid receptor antagonist SR 141716A (20 mg/kg) reversed the effects of 1000 micrograms/kg CP 55,940 on ultrasonic vocalizations and body temperature, but the benzodiazepine receptor antagonist flumazenil (20 mg/kg), the dopamine D1 receptor antagonist SCH 23390 (0.5 mg/kg) and the opioid receptor antagonist naloxone (1 mg/kg) did not. When administered alone, SR 141716A (20 mg/kg) increased pup ultrasonic vocalizations without affecting body temperature or activity. These results indicate that cannabinoids modulate ultrasonic vocalization production in rat pups in a manner that is independent of hypothermia. The increase in ultrasonic vocalizations produced by SR 141716A is one of the first reported behavioural effects of this drug and suggests that the endogenous cannabinoid ligand anandamide may be involved in the regulation of ultrasonic vocalizations.  相似文献   

11.
In humans and laboratory animals, drug withdrawal often is associated with depression-like behaviors. In the present study, rats had unlimited free-choice access to water and a saccharin-containing solution before being subjected to repeated episodes of saccharin deprivation. Saccharin deprivation (1) reduced immobility time in the forced swim test, (2) increased reinforcement rate in rats trained to lever-press under the differential reinforcement of a low-rate (72-sec) schedule of food reinforcement, and (3) lowered intracranial self-stimulation thresholds in a discrete-trial current titration procedure. Taken together, these findings suggest that deprivation from a nondrug reinforcer, saccharin, is not associated with depression-like behaviors. In contrast, saccharin-deprived rats demonstrated improved performance in the behavioral paradigms used here. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

12.
Alcoholism is a complex disorder influenced by interactions between genetic and environmental risk factors. This study examined the influence of isolate housing on ethanol intake in alcohol-preferring (P) and non-alcohol-preferring (NP) rats. Rats were isolate-housed or pair-housed for 8 weeks when between 45 and 96 days old. Ethanol drinking was assessed using a 24-hr preference test (10% ethanol vs. water) and 20-min limited access tests. A behavioral test battery was used to assess anxiety-like, depressive-like, acoustic startle, and motor behavior. Isolate housing increased home cage drinking in both lines and increased limited access drinking selectively in P rats. Isolation also reduced swim test immobility and prepulse inhibition in P rats and increased locomotor stereotypies in NP rats. Taken together, these data demonstrate that Line × Environment interactions influence the effects of isolation. Furthermore, isolation selectively increased ethanol intake in high drinking P rats. This effect was not correlated with changes in other behaviors. Selective enhancement of limited access ethanol drinking in P rats may represent a model whereby genetic liability to excessive drinking is enhanced by specific environmental exposures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

13.
The ethanol withdrawal syndrome includes anxiety as a prominent symptom. Because the extent that specific regions of brain are critical to the generation of this emotional state is unknown, Fos-like immunoreactivity (Fos-LI) was used to associate specific regions of the rat brain with the anxiety component of the ethanol withdrawal syndrome exacerbated by an air puff challenge in rats. Chronic ethanol liquid diet was administered intragastrically for 4 days or by having the rats consume the diet for 14 days. During withdrawal from either treatment protocol, Fos-LI was induced most prominently in forebrain areas, although the midbrain and hindbrain were also represented. Included in these Fos-LI positive regions were many cortical regions, septum, accumbens, claustrum, amygdala, paraventricular nucleus of the thalamus and hypothalamus, hippocampus, locus coeruleus, and central gray. Fos-LI expression differed mostly in intensity between the two treatment and withdrawal protocols, with the gastric protocol producing the greatest Fos-LI induction in most brain regions. The threshold for air puff-induced ultrasonic vocalizations was decreased, and the number of vocalizations was increased and the period of vocalization was extended. These behavioral data indicate that aversively motivated responding in rats during ethanol withdrawal can be readily quantified with the ultrasonic vocalizations test without precipitating convulsive activity. Furthermore, a comparison of the effects of the air puff challenge versus withdrawal on Fos-LI indicated that the behavioral state induced in these two situations share functional neuroanatomical features. Some regions--such as the accumbens core, medial septum, subregions of the amygdala, hippocampus, substantia nigra, and cerebellum--exhibited little Fos-LI during withdrawal and also did not exhibit strong increases after the addition of the air puff challenge. However, other regions-such as the cerebral cortex (medial prefrontal, frontal, cingulate and ventrolateral orbital, claustrum, and tenia tecta), hypothalamus, and locus ceoruleus- exhibited Fos-LI at levels higher than that seen after either the ethanol withdrawal or puff challenge alone. These overlapping patterns of Fos-LI in specific regions of the brain, activated by both ethanol withdrawal and an anxiety provoking behavioral challenge, suggest that specific neuroanatomical sites in brain are associated with the symptom of anxiety observed during the "ethanol withdrawal syndrome."  相似文献   

14.
Pharmacological experiments were conducted to determine the neuronal mechanisms involved in the suppressive effects of the thyrotropin-releasing hormone analog TA-0910 on alcohol intake in alcohol-preferring (P) rats. We previously reported that single intraperitoneal injections of TA-0910 dose-dependently reduced alcohol intake in P rats without altering fluid or total calorie intake; however, after several consecutive, once-daily injections, P rats developed tolerance to the suppressive effects of TA-0910 on alcohol intake and cross-tolerance to like effects of the dopamine D2 agonist bromocriptine, but not to like effects of the serotonin uptake inhibitor fluoxetine. In the present study, rats were injected with vehicle or different doses of the D2 antagonist s(-)-eticlopride (0.01 to 0.05 mg/kg) or the D1 antagonist R(+)-SCH23390 (0.1 to 0.5 mg/kg) and 20 min later with TA-0910 (0.75 mg/kg). Alcohol and water intakes were measured at 2, 4, 6, and 24 hr, and food was measured every 24 hr. Both s(-)-eticlopride and R(+)-SCH23390 produced modest reductions in alcohol intake alone; however, only s(-)-eticlopride antagonized the suppressive effect of TA-0910 on alcohol intake. In related experiments, it was confirmed that the dopamine D3 agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin reduced alcohol intake in P rats, and it was found that tolerance to this effect did not develop during or after seven consecutive once-daily injections. Furthermore, this effect of 7-hydroxy-N,N-di-n-propyl-2-aminotetralin was not diminished in rats made tolerant to the effect of TA-0910 on alcohol intake. These data, those of previous studies, and recent preliminary findings support involvement of dopamine D2, but not D1 or D3 receptors in mediating the suppressive effect of TA-0910 on alcohol intake of P rats.  相似文献   

15.
In 2 experiments, access to a .15% saccharin solution was followed on alternating days by access to a 32% sucrose solution and the same saccharin solution. In Exp 1, rats increased both intake of and preference for a flavored saccharin solution that predicted sucrose, but neither effect was found using a predictive odor cue alone. Exp 2 replicated the predictive flavor results but showed suppression of saccharin intake when environmental cues predicted sucrose. When both flavor and environment predicted sucrose, saccharin intake did not change, but preference for the predictive flavor increased. Discriminative taste cues appear to facilitate the development of preference conditioning, but environmental cues favor negative anticipatory contrast effects. Also, preference conditioning and contrast may develop concurrently and compete for expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

16.
Individual predispositions in emotional reactivity have been suggested as factors involved in the development of alcoholism. To approach this problem, we assessed emotional reactivity in alcohol-naive animals from the alcohol-preferring (AA) and alcohol-avoiding (ANA) rat lines of Alko Ltd. AA rats are known to have higher brain levels of 5-hydroxytryptamine (5-HT) than ANA rats. Emotional reactivity was therefore assessed by an audiogenic immobility reaction (freezing), which is specifically sensitive to and shortened by depletion of 5-HT. The results showed that AA rats of both sexes displayed increased immobility reactions compared to the corresponding sex of the ANA rats. During the period of adaptation to the test cage ANA rats of both sexes showed increased locomotor activity compared to the corresponding sex of the AA rats. Levels of plasma corticosterone did not differ between the rat lines, either during resting or stressful conditions. The present results suggest that a passive, inhibited style of defensive behavior is associated with a high alcohol consumption.  相似文献   

17.
Reanalyses of first-degree biometrical genetic data from previous studies of alcohol preference in the mouse revealed little consistency beyond a basic additive genetic component. A simplified triple-test cross in the rat investigated the genetic architecture of alcohol preference for a 10% (w/v) alcohol solution or water. An initial survey of eight selected and inbred strains identified high- and low-scoring strains, the MNR and the ACI respectively, which were crossed as tester lines to six strains ( the RHA, RLA, TMB, TMD, MNR, and ACI) to produce the required set of largely F1 families. The additive-dominance model proved adequate for males, and directional dominance for low alcohol preference was found on all three measures: alcohol intake, alcohol preference ratio, and alcohol calorie contribution ratio. For females the model was adequate only for alcohol preference ratio, which showed ambidirectional dominance. The relevance of such genetic architecture to an animal model of alcoholism and to the evolution of alcohol drinking in the rat is discussed.  相似文献   

18.
The authors provide initial documentation that juvenile rats emit short, high-frequency ultrasonic vocalizations (high USVs, approximately 55 kHz) during rough-and-tumble play. In an observational study, they further observe that these vocalizations both correlate with and predict appetitive components of the play behavioral repertoire. Additional experiments characterized eliciting conditions for high USVs. Without prior play exposure, rats separated by a screen vocalized less than playing rats, but after only 1 play session, separated rats vocalized more than playing rats. This findings suggested that high USVs were linked to a motivational state rather than specific play behaviors or general activity. Furthermore, individual rats vocalized more in a chamber associated with play than in a habituated control chamber. Finally, congruent and incongruent motivational manipulations modulated vocalization expression. Although play deprivation enhanced high USVs, an arousing but aversive stimulus (bright light) reduced them. Taken together, these findings suggest that high USVs may index an appetitive motivation to play in juvenile rats.  相似文献   

19.
Conducted 2 experiments to examine 70-kHz ultrasonic courtship vocalizations by adult male mice to novel odors following exposure to these odors in infancy and/or adulthood. Exp I, with 72 males, demonstrated that adult males normally do not vocalize to the urine of female rats but would if adult female mice odorized with female rat urine were repeatedly encountered postpubertally. On the other hand, encountering their own mother odorized with female rat urine from birth until weaning did not promote vocalizations to the urine of female rats. Exp II, with 100 males, examined vocalizations to the urine of female mice whose urinary odor was altered by the ingestion of fenugreek, a spice. Greater amounts of vocalization again were seen by males that as adults encountered females that had ingested fenugreek. Again, experience with the novel odor during infancy was not associated with elevated vocalizations during adulthood either to fenugreek-altered urine or to the fenugreek odor itself. Vocalizations to 2 different novel odors occurred only after an adult male had encountered an adult female odorized with the novel odor. (57 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

20.
Notes that after ejaculation, the male rat emits an ultrasonic (22-kHz) vocalization. This sound is produced repeatedly until about 3/4 of the postejaculatory interval has elapsed. In the present experiments, more than 60 male Long-Evans hooded rats were Ss in Exps I and II, and a total of 16 were Ss in Exps III and IV. The occurrence of the vocalization is described, and physiological and behavioral evidence are presented that the postejaculatory vocalization reflects an inhibitory state that underlies the postejaculatory refractory period. The vocalization period was characterized by a predominance of slow-wave, spindling, sleeplike EEG activity. Electrical shock was able to stimulate mating responses only after the cessation of the vocalization period. It is concluded that an absolute refractory period of the postejaculatory interval lasts until the end of the vocalization period and that the time from the termination of the vocalization until the resumption of mating is a relative refractory period. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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