Effects of d-amphetamine and of diazepam on non-punished and punished schedule-induced drinking in rats

Drinking induced in food-deprived rats by a Fixed-Time 1min schedule of food presentation was measured by the amount of water consumed per session and the number of licks per inter-food interval. Subsequently each lick initiated a 10-sec signalled delay in the delivery of food, which led to a decrease in drinking (punishment). With three rats the effects of d-amphetamine (0.25, 0.5, 1.0, 2.0mg/kg) were assessed on non-punished and then on punished drinking. With another three rats, the effects of diazepam (0.5, 1.0, 2.0, 4.0mg/kg) were assessed. The smaller doses of d-amphetamine had no consistent effect on overall measures of non-punished schedule-induced drinking, but the largest dose decreased them. With the signalled delay d-amphetamine increased punished schedule-induced drinking. Non-punished drinking was increased by small doses of diazepam and decreased by the largest dose, but no dose of diazepam affected punished drinking.     

The effects of fenfluramine on schedule-induced drinking in rats

The lever pressing of rats was maintained by a fixed-interval 60 sec schedule of food reinforcement. Water bottles were available during sessions and high levels of schedule-induced drinking developed. Both fenfluramine (0.5, 1.0, 2.0, 4.0, 8.0 mg/kg) and d-amphetamine (0.25, 0.5, 1.0, 2.0 mg/kg) produced dose related decreases in this drinking with d-amphetamine approximately four times as potent as fenfluramine. d-Amphetamine produced large increases in overall rates of lever pressing and greatly decreased the duration of postreinforcement pauses. Fenfluramine exerted similar actions but at all doses studied these effects were much less than the effects of d-amphetamine on these measures.     

Nicotine and schedule-induced drinking in rats

In the first experiment 4 rats developed schedule-induced water drinking during daily 1 hr sessions of a fixed-time 1 min schedule of food pellet delivery. Injections of a range of doses (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg) of nicotine hydrogen tartrate were found to produce a dose related attenuation of water intake. The higher doses also reduced the numbers of entries into the food tray in three rats, while the lowest dose consistently facilitated this behavior in the same animals. In a second experiment schedule-induced water drinking developed in 4 other rats under a similar schedule. Substitution of nicotine solution (0.05 and 0.1 mg/ml) for the water reduced volumes of fluid consumed. However, schedule-induced drinking continued at a rate sufficient for the animals to ing-st average doses of the nicotine salt of up to 8.5 mg/kg. It is concluded that schedule-induced drinking can be used successfully as a method of inducing self-administration of nicotine by rats.     

The effects of d-amphetamine and scopolamine on drinking induced by a multiple schedule

Three food-deprived rats obtained food pellets on a multiple fixed-interval fixed-time schedule. During fixed-interval components a 45 mg pellet was made available for a lever-press every minute (FI 1 min). When the fixed-time component was in operation the lever was retracted and a pellet was delivered every minute (FT 1 min) independent of behaviour. A water bottle was aviilable to each subject and similar levels of schedule-induced drinking developed during the two schedule components. The effects of several doses (0.25, 0.5, 1.0, 2.0 mg/kg) of d-amphetamine and scopolamine were assessed on lever-pressing and drinking maintained by this procedure. Both drugs increased rates of lever-pressing at lower doses and reduced levels of licking and water intake at all doses. The patterning of fixed-interval lever pressing was altered by both drugs increasing the proportion of responses emitted during early parts of the intervals. d-Amphetamine also increased the proportion of licks that occurred during early segments of the interfood intervals, while scopolamine had variable effects on patterns of licking. There were no consistent differences in the effects of the drugs on licking induced by the two schedules.     

Rate-dependency and hyperactivity: methylphenidate effects on operant responding

The two most common treatment for hyperactivity are psychopharmacological regimens and behavior therapy. Although the concurrent use of stimulant medication has been purported to enhance a child's rate of responding under a behavior management program, studies examining the interaction of the two treatments have been unable to confirm this hypothesis. The present investigation sought to examine the effects of differing levels of methylphenidate hydrochloride (Ritalin) upon operant responding with hyperactive children. After an initial drug-free training period, 10 first through fourth grade hyperactive males performed an operant key-pressing task under a mult VR 5 FI 30 sec reinforcement schedule across four randomly determined, double-blind drug conditions (placebo, 5, 10, 15 mg). Only VR responding changed significantly during medication conditions; however, rate-dependent psychostimulant effects were found within both reinforcement schedules. Discrepancies with animal rate-dependency and implications for treatment and future research are discussed. Medication effects on operant responding appear to depend upon the reinforcement schedule and dose employed.     

Antipunishment effects of diazepam on two levels of suppression of schedule-induced drinking in rats

Food-deprived Wistar rats were exposed to a fixed-time (FT) 60-s food delivery schedule until they developed schedule-induced drinking. Rats were matched in pairs according to their licking rates and were designated master or yoked at random. Every fifth lick by master rats was followed by an electric shock during two signalled 5-min periods, which ran concurrently with the food delivery schedule. For the master rats, shock intensities were adjusted to reduce licking to 5-30% (low suppression) or 50-75% (high suppression) of the unpunished licking rates. Yoked rats received the same shocks as master rats, but independently of their own licking. The drinking by yoked animals was not decreased by the presentation of these lick-independent shocks. Diazepam (0.3-10.0 mg/kg) was studied for its effects on punished and nonpunished schedule-induced drinking. Intermediate doses of the drug increased the punished behavior of master rats, but only when schedule-induced drinking was highly suppressed. Diazepam dose dependently decreased licking rates in all other conditions. The antipunishment effects of benzodiazepines may depend on the level of suppression of schedule-induced drinking, and this is in keeping with the results of other experimental preparations where behavior was under aversive control.     

d-amphetamine and adjunctive drinking in rats

In the first experiment four food-deprived rats developed high levels of adjunctive water drinking during daily sessions of intermittent food pellet delivery. When the water was removed and a solution of d-amphetamine sulfate (0.01 mg/ml) put in its place, adjunctive drinking was disrupted towards the end of each session although the rats ingested doses of approximately 0.5 mg/kg daily for over 40 sessions. Consumption of the d-amphetamine solution was increased by injections of several doses of -methyl-p-tyrosine (AMPT). In a second experiment injections of d-amphetamine (0.25, 0.5, 1.0, 2.0 mg/kg) were found to reduce adjunctive water consumption in six rats. It was also found that the actions of the two highest doses of d-amphetamine were reduced by pretreatment with a dose of AMPT (100 mg/kg), which itself slightly reduced levels of drinking. These results suggest that, although adjunctive drinking may be a useful technique for inducing rats to self-administer d-amphetamine, the amount of drug consumed is limited by a direct action of the drug on drinking.     

Effects of d-amphetamine, diazepam and buspirone on schedule-induced polydipsia suppressed by response-dependent and response-independent shock

Food deprived Wistar rats were exposed to a fixed time 60 s food schedule until they developed schedule-induced polydipsia. Rats were matched in pairs according to their licking rate, being designated experimental or yoked control at random. Every fifth lick by experimental rats was then followed by an electric shock (0.05, 0.1, or 0.2 mA) while the food schedule continued in operation. Yoked-control rats received the same shocks as experimental rats, but independently of their own licking. Drugs were then tested on the suppressed rates of licking. Diazepam (0.5-2.0 mg/kg) increased punished schedule-induced polydipsia, a result not observed in yoked controls. No increases in the licks per minute of experimental or control animals were found after d-amphetamine (0.25-4.0 mg/kg) or buspirone (0.5-8.0 mg/kg). In comparison with previous results it is concluded that the antipunishment effects of drugs on schedule-induced behaviour depend on the type of punishment contingency.     

Characteristics of ethanol drinking patterns under schedule-induced polydipsia

Rats were induced to consume concentrations of ethanol between 5% and 10% (w/v) using the schedule-induced polydipsia technique. Although the substitution of ethanol solutions for water disrupted the usual post-pellet pattern of drinking, large amounts of ethanol were consumed and sound-induced convulsions were observed during ethanol withdrawal. In subsequent experiments, other rats chose 5% and sometimes 10% ethanol solutions over water where both water and ethanol were freely available during the first session of exposure to ethanol. Convulsions and wild running behavior could be observed in some of these rats after only 8 days of drinking, even though ethanol was freely available at all times. Use of the schedule-induced polydipsia technique served to bring the rats into early contact with the ethanol, but rats that received the same number of food pellets in a dish rather than by the schedule drank almost as much ethanol as did the rats receiving ethanol by the schedule. Rats with free access to food pellets drank very little ethanol.     

Attenuating the rate-decreasing effects of phenylpiperidine analgesics by pentobarbital

The ability of pentobarbital, diazepam, and chlorpromazine to attenuate the rate-decreasing effects of a high dose (10 or 30 mg/kg) of meperidine was tested in pigeons responding under a multiple fixed-ratio, fixed-interval schedule of food presentation. Pentobarbital (10 mg/kg) attenuated the meperidine-induced rate decreases, whereas diazepam (0.3–3 mg/kg) or chlorpromazine (3–30 mg/kg) did not reliably attenuate the response rate decreases. The combination of 10 mg/kg of pentobarbital and meperidine resulted in a marked disruption of the pattern of responding in the fixed-interval component of the multiple schedule. Pentobarbital (1, 3, 10, and 17.5 mg/kg) was also tested in combination with rate-decreasing doses of normeperidine (17.5 mg/kg), anileridine (10 mg/kg), alphaprodine (10 mg/kg), and fentanyl (0.3 mg/kg). Pentobarbital reliably attenuated the rate-decreasing effects of normeperidine, anileridine, and alphaprodine, but not the rate decreases induced by fentanyl.     

Differential effects of morphine and LiCl on schedule-induced polydipsia

Lithium chloride (LiCl) and morphine both produce a conditioned taste avoidance response, while only LiCl is able to elicit a conditioned rejection response (taste reactivity), indicating that the effects of conditioning are drug and preparation dependent. The present experiments extend this assessment to another behavioral preparation, schedule-induced polydipsia (SIP), by examining the ability of LiCl and morphine to produce conditioned suppression of nonregulatory drinking. In Experiment 1, schedule-induced saccharin consumption was followed by LiCl or morphine (at doses comparably effective in conditioning taste avoidance under water deprivation) or by the distilled water vehicle. Although both LiCl and morphine suppressed SIP, morphine produced a significantly weaker suppression than did LiCl. Using a massed feeding design in which animals received all their food pellets in a single meal, Experiment 2 determined that LiCl and morphine were equally effective in suppressing consumption, indicating that the differential effects seen under SIP were due to the schedule of spaced food pellet deliveries. The basis for the differential effects of LiCl and morphine on SIP may be a function of an increase in the reinforcing properties of drugs of abuse (such as morphine) within this procedure that mask the acquisition and/or display of the conditioned suppression. If so, then this procedure may be useful in assessing the reinforcing properties of such drugs.     

Effects of selective central muscarinic blockade on schedule-controlled behavior and on the rate-decreasing effects of physostigmine

N-(4-diethylamino-2-butynyl)-succinimide, or DKJ-21, is a muscarinic receptor antagonist with a high degree of selectivity for the central nervous system. In the present study of 6 rats maintained under a fixed-interval 50-sec schedule of food reinforcement, atropine and methylatropine reduced responding in a dose dependent manner, while DKJ-21 had little or no effect. Our findings suggest that the suppression caused by atropine and methylatropine may be the result of the dry mouth induced by these agents. Doses of DKJ-21 which had no effect on schedule performance antagonized the ratelowering effects of physostigmine in all of the animals. Neither atropine nor methylatropine consistently antagonized the inhibitory effects of physostigmine. Some antagonism may be inferred, however, from the findings that response rates were suppressed less by combinations of atropine and physostigmine than by either drug alone.     

Cholecystokinin potentiates the rate-decreasing effects of morphine on schedule-controlled behavior in rats

In one component of a multiple schedule, responding (licking in rats) was reinforced under a fixed-ratio (FR 50) schedule of water presentation. In the other component, responding had no programmed consequences (timeout). Each session consisted of four 10-min timeout components alternating with four FR components. In general, increasing cumulative doses of morphine (3.2-18 mg/kg) produced a dose-dependent decrease in the overall rate of responding. In one subject, cholecystokinin (CCK) alone (10-32 micrograms/kg) produced dose-dependent decreases in rate in the first component, while in the other two subjects relatively little decrease in rate occurred. When these doses of CCK were given as a pretreatment before morphine, the decrease in overall response rate was greater than that found with morphine alone. This interaction was most noticeable at the lowest dose of morphine where CCK produced a dose-dependent "potentiation" of the rate-decreasing effects. Although the potentiation of CCK was not as evident at the intermediate doses of morphine, there were instances in which the rate-decreasing effects produced by the combination were greater than those expected from addition of the effects of CCK and morphine alone. In contrast, when naltrexone (1 mg/kg) was given as a pretreatment, little or no rate-decreasing effects were produced by the cumulative doses of morphine. Furthermore, pretreatment with naltrexone and the administration of a higher dose range of morphine indicated the dose-effect curve for morphine had shifted approximately 3/4 log-units to the right.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time-response effects of pimozide on operant behavior and schedule-induced polydipsia

Previous research has indicated that the administration of specific doses of pimozide results in the suppression of the acquisition of schedule-induced polydipsia in rats while not affecting operant behavior. The purpose of this study was to determine if these results were due to a specific action of pimozide on schedule-induced polydipsia or if they were due to an insufficient presession time of drug administration. Pimozide at 1.0 mg/kg was administered to three groups of rats at either 30, 60 or 120 minutes presession with control subjects receiving administration of the drug vehicle also at these times. The results of the study were that both operant behavior and the acquisition of schedule-induced polydipsia were affected in a nondifferential and time-dependent manner by pimozide. It was also found that pimozide caused an alteration in the temporal pattern of both schedule-induced polydipsia and operant responding. This latter result appears to have been caused by a disruption in sensorimotor integration due to the dopamine blocking properties of pimozide.     

Selective suppression of schedule-induced ethanol drinking by antialcoholic drugs in rats

Effects of disulfiram and calcium cyanamide, antialcoholic drugs, on schedule-induced ethanol drinking as well as on schedule-controlled response (lever-pressing) under a fixed interval 1 min schedule of food reinforcement were investigated in Wistar strain rats. When ethanol solution was available, the schedule-induced ethanol drinking decreased depending on the ethanol concentration (2-8%). However, the dose of ethanol intake during the 1 hr experimental session was at maximum (2.8 g/kg) when 4% ethanol solution was available. Thereafter, 4% ethanol solution was used in the experiment for studying the effects of disulfiram and calcium cyanamide on the schedule-induced ethanol drinking. Disulfiram (100-200 mg/kg, p.o.), pretreated at 1 hr before the start of the experiment, tended to suppress schedule-induced water drinking. However, the same treatment of calcium cyanamide (5-10 mg/kg, p.o.) did not produce a marked change in it. In contrast, disulfiram (100 and 200 mg/kg) and calcium cyanamide (5 and 10 mg/kg) markedly suppressed schedule-induced ethanol drinking without eliciting a marked change in schedule-controlled response. The present results suggest that both disulfiram and calcium cyanamide selectively suppress ethanol drinking in rats.     

The effects of d-amphetamine on risk taking

Summary The effect of d-amphetamine on the risk-taking behavior of penitentiary inmates was investigated, utilizing a gambling situation involving cigarettes. The experimental situation consisted of choices between alternative gambles involving different amounts of risk. The 29 men served as their own controls, with the number of high-risk choices made by each subject when under drug (10 mg d-amphetamine sulfate, orally) being compared with the number of choices made during his placebo session. The difference was significant in the direction of increased risk-taking under the drug. The results are interpreted as offering tentative support to the hypothesis that d-amphetamine increases risk-taking, although alternative interpretations are provided.The author thanks W. M. Lepley, J. H. Grosslight, and the late S. Siegel of The Pennsylvania State University, and also H. M. Janney, Medical Director of the U.S. Bureau of Prisons, and F. T. Wilkinson, Warden, and the staff of the Northeastern States Federal Penitentiary, for granting access to the subject population.     

Changes in schedule-controlled response and schedule-induced drinking after cholinergic blockers in rats

The effects of the tertiary cholinergic blockers atropine sulfate (AT) and scopolamine hydrobromide (SCOP), and the quaternary cholinergic blockers atropine methylnitrate (AT-Mt) and scopolamine butylbromide (SCOP-Bt), on operant response (lever-pressing) and adjunctive drinking in the rat developed under a fixed interval (FI) 1.5 min food reinforcement situation were investigated. The tertiary compounds, particularly SCOP, increased total responses, and produced a dose-related decrease in the index of curvature (IC) for local rates of response during the FI. The quaternary compounds, however, did not produce changes in the total responses and the IC for local rates of response. AT, AT-Mt and SCOP suppressed adjunctive drinking, while SCOP-Bt did not. AT and SCOP, but not AT-Mt and SCOP-Bt, decreased the IC for local rates of drinking. AT-Mt suppressed drinking at a uniform rate throughout the FI. In addition, several doses of AT and SCOP tended to increase licking counts at the drinking spout per 1 ml water intake. The present results suggest that central cholinergic blockade increases the response and suppress adjunctive drinking, and that the peripheral cholinergic blockade suppresses only adjunctive drinking. Moreover, central cholinergic blockade may produce changes in the patterns of response and drinking during the FI, and in the manner of drinking at the drinking spout.     

Differential effects of d-amphetamine and scopolamine on the ontogeny of rearing

Although rearing is ontogenetically an important behavior, very little is known about the neural bases of rearing. The role development of catecholaminergic and cholinergic neurons play in the ontogeny of rearing was investigated by examining rearing in infant, adolescent, and adult rats following various doses of d-amphetamine (an indirectly acting catecholaminergic agonist) and scopolamine (a cholinergic muscarinic receptor antagonist). d-Amphetamine increased rearing in infants but not in adolescents and adults. These findings suggest that activation of catecholaminergic neurons increases rearing in infants but not in adolescents or adults. Scopolamine increased rearing in adolescents and adults but not in infants, indicating that blocking transmission of cholinergic neurons increases rearing in only older rats.     

Behavioural and pharmacological specificity of the effects of drugs on punished schedule-induced polydipsia

Wistar rats were exposed to a multiple fixed-time 30-s food delivery schedule, with an on/off tone signalling the two components. Animals were matched in accordance with the levels of schedule-induced polydipsia. Drinking was then punished in one of the components: half of the rats received lick-dependent 10-s signalled delays and the other half lick-dependent electric shocks. The intensities of the shocks were adjusted to reduce behaviour by the same amount as the delays in food presentation. Unpunished components were used as yoked-control conditions, by presenting delays or shocks independently of the animals' behaviour. D-Amphetamine (0.3-2.0 mg/kg) and cocaine (1.0-10.0 mg/kg) dose-dependently increased (although only slightly) and then decreased schedule-induced polydipsia punished with lick-dependent delays in food presentation, a result not observed in control conditions or when the behaviour was suppressed by lick-dependent electric shocks. Diazepam (1.0-17.0 mg/kg) and pentobarbital (3.0-17.0 mg/kg) dose-dependently increased and then decreased only the schedule-induced drinking punished with lick-dependent shocks. Buspirone (0.1-1.0 mg/kg) and morphine (2.0-5.6 mg/kg) showed either no specific effects or further suppressed schedule-induced drinking. Results of these and previous experiments suggest that the antipunishment effects of drugs depend not only on the precise nature of the drug, but also on the manner in which the behaviour is maintained.