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PubMed1976

Schedule-induced oral self administration of etonitazene.

Rats were induced to drink either a saline-etonitazene solution or a saline solution with a schedule-induced polydipsia paradigm. When water was freely available, the rats continued to drink the saline solution or the saline-etonitazene solution, rather than the water. When the locations of the solutions were switched, the rats that were drinking saline switched to water (drank at the usual location), but the rats that were drinking saline-etonitazene continued to drink the saline-etonitazene solution (drank from the bottle at the other location). Naloxone administration temporarily eliminated the drinking of saline-etonitazene solution, but not that of saline solution.

Administration, Oral↗
PubMed1976

Ethanol elimination rates in normal and ethanol dependent animals.

Ethanol elimination rates were determined in rats using an intravenous route of ethanol administration after several experimental manipulations. Twenty-four hr food deprivation resulted in a 30% reduction to 35 mg/100ml blood/hr in elimination rate from a non-deprived rate of 50 mg/100 ml blood/hr. After 2 months of ethanol drinking (5% v/v), 24 hr starvation resulted in only a 10% reduction in elimination rate (45 mg/100 ml blood/hr), and did not increase the non-food-deprived rate (49.2 mg/100 ml blood/hr) over that obtained in the above animals' drinking water rather than 5% ethanol. Animals which chronically overdrank ethanol or water for 3 months on a schedule-induced polydipsia procedure, known to result in ethanol physical dependence, showed a decreased rate of ethanol elimination (37.9 mg/100 ml blood/hr for water drinkers) in the non-food-deprived condition. By providing 750 mg of liver powder daily as a food supplement in the ethanol overdrinking regimen, the ethanol elimination rate remained at a rate comparable to the normal animal (48.4 mg/100 ml blood/hr).

Alcohol Drinking↗
PubMed1976

Schedule induced behavior: a review of its generality, determinants and pharmacological data.

Adjunctive or schedule induced behavior can be defined as an increase in the frequency of occurrence of an unreinforced behavior in the presence of conditions requiring an intermittent reinforced response, compared with the frequency of that behavior when no intermittent response is required. Although recognition has been given to the occurrence of other schedule induced behaviors it has most frequently been studied as schedule induced polydipsia in a rat on a food delivery schedule. In the present paper recent work on other schedule induced behaviors is reviewed including behaviors occurring in conjunction with nonconsumatory schedule parameters. These range from wheel running in the rat to game playing and maze solving in humans. This paper is also concerned with the review of pharmacological variables including the effects of peripheral and central administration. It is concluded that there may be either quantitative or qualitative differences in drug effects when schedule induced drinking is compared with deprivation induced drinking. A general activation theory [61] that adjunctive behaviors is the result of an increase in the excitability of motor pathways which lead through the lateral hypothalamus can account for the data presented in this and earlier reviews but is too broad in its conception to make specific predictions about the relationships between schedule induced and schedule controlled behavior.

Animals↗
PubMed1977

Establishment of etonitazene as a reinforcer for rats by use of schedule-induced drinking.

Drinking of etonitazene HCl by 6 rats was studied during daily 4-hr sessions. Five related experiments were conducted sequentially. In the first experiment schedule-induced polydipsia was established. Subsequently, etonitazene concentrations (1.25, 2.5 and 5.0 microgram/ml) were substituted for water, and intake of large quantities of the drug occurred. In the second experiment the concurrent food reinforcement schedule was discontinued and lever presses maintained by etonitazene (5 microgram/ml) persisted. In the third experiment the number of lever presses, required per dipper presentation of etonitazene (5 microgram/ml) was increased, and rate of lever pressing increased directly with the response requirement whereas number of dipper presentations remained constant. In the fourth experiment water was substituted for the 5 microgram/ml etonitazene solution. Water responding declined to low rates, but when etonitazene was reintroduced, responding increased to previous levels. Thus, etonitazene (5 microgram/ml) was functioning as a positive reinforcer. In the final experiment, progressive increases in the etonitazene concentration (5, 10, 20 and 40 microgram/ml) resulted in both systematic decreases in response rate and increases in quantity (microgram) consumed.

Animals↗
PubMed1978

Control of polydipsic drinking by a taste aversion procedure.

Rats were given daily sessions with free access to food and saccharin flavored water. After fluid consumption had stabilized food was delivered once every minute. Water was always available in the home cage. All rats showed the marked increase in fluid consumption known as schedule-induced polydipsia. The rats were then poisoned with lithium chloride after each of three sessions in an attempt to condition a taste aversion to the saccharin. On recovery from the toxicosis all rats showed first a reduction and then a recovery in saccharin intake. To establish the nature of this effect, the rats were poisoned after saccharin consumption in the home cage. Again there was a marked reduction in polydipsic drinking in the experimental chamber. These results indicate that common incentive mechanisms govern normal and polydipsic drinking and stand in contrast to published results pointing to different drive systems in the brain mediating normal and polydipsic drinking.

Animals↗
PubMed1987

Effect of dopamine agents on schedule- and deprivation-induced drinking in rats.

The dopamine agonist, apomorphine, or its antagonist, haloperidol, was administered to rats whose drinking was induced by fixed-interval schedules of pellet delivery or by water deprivation. The first study revealed that both drugs produced dose-dependent decreases in bar-pressing and schedule-induced polydipsia (SIP). At higher doses, haloperidol also depressed the rate of pellet delivery. The second study demonstrated that the suppression in SIP obtained in the first study was primarily due to the direct effect of the drugs and not to changes they produced on the underlying food reinforcement schedule. The third study showed that both drugs suppressed water deprivation-induced drinking during a ten-minute session. Apomorphine delayed the onset of drinking, while haloperidol accelerated the cessation of drinking. The results indicated that apomorphine produced motor deficits that interfered with consummatory behavior, and that haloperidol interfered with the sensory feedback necessary to sustain consummatory behavior.

Animals↗
PubMed1987

Oral self-administration of cocaine: chronic excessive intake by schedule induction.

Rats were exposed to daily 3-hr schedule-induced polydipsia sessions (fixed-time 1 min food-pellet delivery) with a cocaine hydrochloride solution as the available session fluid. Cocaine intake level (mg/kg) was a direct function of solution concentration (0.02-0.2 mg/ml). In a second experiment with 0.15 mg/ml cocaine solution available, mean daily session cocaine intake remained constant at about 40 mg/kg over the 5-week period of the experiment. Post-session serum samples of animals drinking either 0.15 or 0.2 mg/ml cocaine solution yielded serum cocaine values that were similar to those producing subjective "highs" in coca-leaf chewers and experienced users of cocaine. The schedule-induction technique can be used to induce the intake of drug solutions, including those which perhaps taste bitter, so that chronic and pharmacologically significant consequences ensue.

Animals↗
PubMed1987

Development of physical dependence on midazolam by oral self-administration.

Groups of rats drank either a solution of the ultrashort-acting benzodiazepine midazolam or water under schedule-induced polydipsia conditions in chronic, daily, 3-hr sessions. In Experiment 1, the physical dependence status of animals was tested after 9 months by the precipitated withdrawal method using the benzodiazepine-blocking agent Ro 15-1788 and by exposure to a brief audio stimulus at 1.5, 12 and 24 hr following drug withdrawal. Ro 15-1788 failed to produce withdrawal signs, while the audio stimulus plus withdrawal did. In Experiment 2, similar groups were periodically tested for susceptibility to audiogenically-induced seizures at 3, 6, 12, 15, 18, 21, 24 and 26 weeks 90 minutes after their drug or vehicle intake sessions. In the midazolam-drinking group, physical dependence developed at about 12 weeks and increased in severity over the course of the study. Serum measures confirmed that continuous elevation of drug and active metabolite levels are not necessary for the development of physical dependence. A chronic, daily, single elevation of a few hr was sufficient.

Administration, Oral↗
PubMed1989

Antidepressant effects of rolipram in a genetic animal model of depression: cholinergic supersensitivity and weight gain.

The effects of rolipram, a new generation antidepressant which is a selective inhibitor of phosphodiesterase, on the selectively bred Flinders Sensitive Line (FSL) of rats, a genetic animal model of depression, was studied. Acutely, rolipram produced comparable decreases in temperature and activity in the FSL and the Flinders Resistant Line (FRL) rats. Upon chronic treatment there was a trend for rolipram to counteract the shock-induced suppression of activity in the FSL rats, suggesting an antidepressant-like effect. However, both groups gained a significant amount of weight, which appeared to be associated with polydipsia and polyuria. In addition, both groups were significantly more affected by the muscarinic agonist, oxotremorine, than their vehicle-treated counterparts. Thus, the FSL rats, which are genetically supersensitive to cholinergic agonists, are even more sensitive following chronic treatment with rolipram. These unexpected findings suggest that rolipram may not be appropriate as an antidepressant for humans because of undesirable side effects.

Albuterol↗
PubMed1989

Schedule-induced chlordiazepoxide intake: differential effect of cocaine and ethanol histories.

Groups of rats were given differential histories of drinking either water, cocaine (0.15 mg/ml), or ethanol (2.5%) solutions under fixed-time (FT) 1-min schedule-induced polydipsia conditions in daily, 3-hr sessions. The session solution for all groups was then changed to chlordiazepoxide (0.25 mg/ml), and after daily session intakes had stabilized, FT values of 3 and 5 min were probed for single sessions. Probe-session chlordiazepoxide intakes were greater for the Ethanol History Group than for Cocaine History and Water History Groups. Previous research showed that probe conditions elevated intakes for agents with abuse potential (cocaine, ethanol, midazolam), but not for those lacking such potential (water, chlordiazepoxide, flurazepam). The present study demonstrated that a history of ethanol overindulgence yielded elevated probe intakes for chlordiazepoxide, while a history of cocaine or water overindulgence did not. This is consistent with animal and human evidence indicating that a history of either alcohol or sedative abuse increases the probability that benzodiazepines will function as reinforcers and/or be abused.

Chlordiazepoxide↗
PubMed1992

Effects of D1 and D2 dopamine antagonists on behavior of polydipsic rats.

The behavioral and neurochemical effects of SCH3390 (SCH), a dopamine (DA) D1 antagonist, and haloperidol (HAL), a DA D2 receptor antagonist, on schedule-induced polydipsia (SIP) were examined. Once animals were made polydipsic, a vehicle or one of three doses of SCH or HAL were administered to seven groups of rats in a series of three five-session blocks in a drug condition, no-drug condition, drug condition design. Detailed behavioral measures and brain regional levels of monoamine neurotransmitters and their major acidic metabolites were analyzed. The volume of water consumed and the percent of time spent drinking was reduced dose dependently by both SCH and HAL. As drinking decreased, the time spent chewing increased for both drugs. The total amount of time animals engaged in all oral behaviors was not changed, suggesting that chewing was substituted for drinking. Neurochemical analysis revealed that HAL increased striatal DA significantly. The polydipsic paradigm may be an advantageous model for examining neuroleptics due to SIP's sensitivity to extrapyramidal side effects.

Animals↗
PubMed1992

Oral cocaine self-administration: relation of locomotor activity to pharmacokinetics.

Rats were exposed to daily schedule-induced polydipsia sessions in which solutions of cocaine HCl were available. Both cocaine solution concentration (0.08-0.32 mg/ml) and session duration (0.25-3 h) were varied to determine their effects on locomotor activity rate. Additional animals were used to determine the effect of session length on serum cocaine and metabolite levels when drinking 0.32 mg/ml cocaine solution. Changes in locomotor activity rate were related to serum cocaine concentration by a linear concentration-effect model. By estimation from the linear model, the serum cocaine concentration threshold for increasing locomotor activity was about 0.01 microgram/ml. Under these schedule-induction conditions, there was no evidence for the development of acute tolerance to the locomotor-stimulating activity of cocaine.

Animals↗
PubMed1995

Stimulus control of addictive behavior: persistence in the presence and absence of a drug.

Rats were exposed daily to a food schedule-induced polydipsia condition, in which water and 0.16 mg/ml cocaine solution were available concurrently, with the cocaine solution indicated by a discriminative stimulus (SD) light. The cocaine solution was preferred, and the preference was maintained when the SD was gradually eliminated by fading its intensity. For a second group, if cocaine concentration was the stimulus gradually eliminated, preference for the resulting solution (water) indicated by the SD was stably maintained. For two additional groups, if either the light SD or the cocaine stimulus was removed abruptly rather than gradually, few animals retained preferences. These studies reveal the importance of establishing strong stimulus control for the initiation and persistence of drug abuse behavior.

Animals↗
PubMed1994

Acute and chronic nicotine effects on multiple-schedule behavior: oral and SC routes.

For rats responding on a 3 h FI 4 min FR 20 schedule of food reinforcement, presession SC nicotine doses (0.1-0.8 mg/kg) produced depression in all responding followed by stimulation of FI responding that was dependent upon both time and dose. With daily presession 0.8 mg/kg SC nicotine injections for 9 days, no tolerance to the depressive or stimulatory effects of nicotine occurred. When nicotine solutions were orally self-administered by presession exposure to 3 h of schedule-induced polydipsia, the subsequent FR responding was unaffected, but the degree of FI response stimulation and its duration occurred in a dose-related fashion (1.18-4.10 mg/kg). Prolonged daily sessions of oral nicotine self-administration provide a technique for investigating the effects of chronic exposure to nicotine. The postingestive effects of nicotine reveal stimulatory effects that last for at least 3 h.

Administration, Oral↗
PubMed1996

Metabolic mapping of the effects of chronic voluntary ethanol consumption in rats.

The 2-[14C]deoxyglucose method was used to examine the effects of chronic, voluntary ethanol consumption on rates of local cerebral glucose utilization (LCGU). LCGU was measured in male Long-Evans rats immediately following the completion of a 60-min schedule-induced polydipsia drinking session. Three groups of animals were examined: animals with a history of ethanol consumption that received ethanol on the test day (ethanol-ethanol), animals with a similar ethanol history that were presented with water on the test day (ethanol-water), and a control group that received water throughout the experiment (water-water). Ethanol consumption on the test day resulted in a highly discrete pattern of metabolic changes, with significant decreases in glucose utilization in the hippocampal complex, habenula, anterior ventral thalamus, and mammillary bodies, whereas increases were observed in the nucleus accumbens and locus coeruleus. Rates of LCGU in the ethanol-water group were increased throughout all regions of the central nervous system examined, indicating that the long-term consumption of moderate ethanol doses that do not produce physical dependence can cause significant changes in functional brain activity.

Alcohol Drinking↗
PubMed1995

Termination of pregnancy in dogs by oral administration of dexamethasone.

Dexamethasone was administered orally for 7.5 or 10 d to each of 20 pregnant bitches beginning at an estimated 28 to 51 d of gestation, using 1 of 2 dose regimens. Five bitches were given dexamethasone 3 times a day for 10 d, with the highest dose of 0.2 mg/kg for 5 d and then at progressively decreasing doses of 0.16-0.02 mg/kg for 5 d. The 15 remaining bitches were given dexamethasone 2 times a day for 7.5 d, increasing from 0.1 to 0.2 mg/kg over the first 3 administrations, then remaining at 0.2 mg/kg on Days 2 to 5, and decreasing from 0.16 to 0.02 mg/kg over the last 5 administrations. The side effects, including mild polydipsia and polyuria, disappeared when treatment was discontinued. Depending on the stage of pregnancy, uterine contents were either resorbed or aborted, or both. Pregnancy was terminated within 2 to 16 d after the start of treatment in all treated bitches, at 2 to 5 d of treatment in 2 of 3 bitches treated at 40 to 51 d of pregnancy, and at 0 to 4 d after the end of treatment in most of the 17 bitches treated at 28 to 35 days of pregnancy. Oral administration of dexamethasone appears to be a potentially useful pharmacologic treatment for the termination of unwanted pregnancy in the bitch.

Journal Article↗
PubMed1996

Bradykinin excretion is increased in severely hyperglycemic streptozotocin-diabetic rats.

The renal kallikrein-kinin system (KKS) was studied in pair-fed streptozotocin (STZ)-induced diabetic rats and compared with age-matched controls. Twelve weeks after STZ injection, rats were normotensive, showed hyperglycemia, proteinuria, polydipsia and reduced glomerular filtration rate (GFR) and body weight. The activities of urinary prekallikrein (PKLK) and kallikrein (KLK) were reduced accompanied by an up to 3-fold increase of bradykinin (BK) excretion compared to controls. The increased BK excretion suggests that the renal KKS in STZ-diabetes is activated and that the reduction in urinary PKLK and KLK activity may be due to an increased consumption of these enzymes or to a negative feedback mechanism. The stimulation of the renal KKS in STZ-diabetes could reflect an attempt of the organism to balance glomerular hypertension.

Animals↗