Effects of RO 15-4513 and FG 7142 alone and in combination with ethanol on avoidance in the rat

Rats were trained on a complex avoidance schedule in which responses on one lever postponed shock and responses on another lever occasionally (variable-interval 45 sec schedule) produced 2 min periods of timeout from avoidance. As shown in previous experiments, ethanol (1.5 or 2.0 g/kg) produced an increase in timeout responding relative to avoidance lever rates. These effects were attenuated in five of the six rats by 6 mg/kg RO 15-4513, a dose that did not produce consistent intrinsic effects. In contrast, FG 7142 (10 mg/kg) reliably reversed ethanol effects in only one of the six rats tested. These results support the notion that RO 15-4513 possesses specific ethanol antagonist properties.     

Variable-interval schedules of timeout from avoidance: effects of anxiolytic and antipsychotic drugs in rats

Concurrent performances were studied in rats under conditions where responses on one lever postponed shock on a Sidman avoidance schedule and responses on another lever produced periods of signaled timeout from avoidance on a variable-interval schedule. Chlorpromazine decreased rates of responding on both the timeout and avoidance levels to about the same extent. The effects of chlordiazepoxide and CGS 9896 depended upon the event maintaining responding. Both drugs increased responding on the timeout lever at doses that concurrently decreased responding on the avoidance lever. Thus, the novel anxiolytic CGS 9896 produced effects that closely resembled those of the benzodiazepine anxiolytic, chlordiazepoxide. Like chlorpromazine, buspirone decreased both avoidance and timeout responding. Despite the documented anxiolytic properties of buspirone, its actions here were unlike those of the other anxiolytic drugs tested. Nonetheless, the differentiation between drugs obtained with the timeout from avoidance procedure indicates its utility for behavioral pharmacology.     

Variable-ratio schedules of timeout from avoidance: effects of anxiolytic drugs

Concurrent performances in rats were studied under conditions where responses on one lever postponed shock on an unsignaled avoidance schedule, and responses on another level produced periods of signaled timeout from avoidance on a variable-ratio schedule. This procedure resulted in relatively high rates of responding on the timeout lever, and provided a baseline which permitted simultaneous evaluation of drug effects on two different types of negative reinforcement (shock postponement vs timeout). Chlordiazepoxide and ethanol selectively increased responding on the timeout lever at low doses, while higher doses decreased responding on both levers. Two 5-HT(1A) agonists, buspirone and 8-OH-DPAT, had different effects. Buspirone decreased responding across all effective doses, but 8-OH-DPAT increased responding on both the timeout and avoidance levers, with greater increases noted in responding maintained by timeout. These results replicate and extend previous findings, and support the notion that traditional anxiolytic drugs like chlordiazepoxide and ethanol may increase the reinforcing properties of escape from an avoidance schedule. Differences between the behavioral effects of buspirone and 8-OH-DPAT may reflect differential activity at the 5-HT(1A) receptor or the dopaminergic properties of buspirone.     

Distinctive behavioral effects of the pyrazoloquinoline CGS 8216 in squirrel monkeys

The behavioral effects of the pyrazoloquinoline CGS 8216 were studied in squirrel monkeys trained to respond under a fixed-interval (FI) schedule of food presentation. Dose-effect curves were determined by administering cumulative doses IV during timeout periods that preceded sequential components of the FI schedule. CGS 8216 (0.1-3.0 mg/kg) produced dose-related decreases in the rate of FI responding. In comparison, diazepam (0.1-3.0 mg/kg) had biphasic effects under identical conditions: intermediate doses increased the rate, whereas high doses decreased the rate of FI responding. Pretreatment with the benzodiazepine antagonist Ro 15-1788 (3.0 or 5.6 mg/kg) attenuated the decreases in response rate normally produced by high doses of CGS 8216. The behavioral effects of CGS 8216 were not altered systematically by pretreatment with either diazepam (0.3-3.0 mg/kg) or the alpha 2-adrenergic agonist clonidine (0.01-0.03 mg/kg). The results suggest that CGS 8216 has benzodiazepine inverse agonist effects on schedule-controlled behavior of squirrel monkeys. CGS 8216 can, however, be distinguished from inverse agonists of the beta-carboline type on the basis of its effects in the presence of diazepam or clonidine.     

Opioid drugs and timeout from avoidance

The effects of μ agonists fentanyl, methadone and morphine and kappa agonist U50,488 on behavior maintained by negative reinforcement were determined. Rats were trained on concurrent schedules in which pressing one lever postponed shock on a Sidman avoidance schedule and pressing the other lever produced signaled periods of timeout from avoidance on variable-ratio schedules. All of the μ agonists decreased responding maintained by timeout from avoidance at doses that increased or did not affect avoidance rates. The kappa agonist U50,488 decreased response rates in some rats, but increased responding in others. In no case was a selective reduction in responding on the timeout lever produced by U50,488. Thus, the previously reported selective decreases in timeout responding by morphine are also produced by μ agonists fentanyl and methadone, but not by kappa agonist U50, 488.     

Behavioral effects of CGS 8216 alone,and in combination with diazepam and pentobarbital in dogs

Beagle dogs (N=3) responded under a multiple fixed-interval (FI) 300 sec, fixed-ratio (FR) 30 schedule of food presentation. The pyrazoloquinoline derivative CGS 8216, given either intravenously (0.01–3.0 mg/kg) or orally (0.1–30.0 mg/kg) had little effect on either the rate or temporal pattern of responding during either component. Both diazepam (0.3 to 17.5 mg/kg, PO) and pentobarbital (0.1–17.5 mg/kg, PO) produced qualitatively similar effects on behavior. Rates of responding during the FI components first increased, then decreased with increasing doses; both drugs produced only dose-related decreases in the rate of responding during the FR components. CGS 8216 antagonized some of the behavioral effects of diazepam; FI and FR response rates returned to baseline, however the effects of diazepam on quarter-life values were not appreciably altered by CGS 8216. The effects of pentobarbital on schedule-controlled responding were not antagonized by CGS 8216. These results indicate CGS 8216 is a selective benzodiazepine antagonist that does not produce benzodiazepine-like behavioral effects.     

Attenuation of the biphasic effects of ethanol on avoidance extinction by RO 15-4513 in rats

Ethanol had biphasic effects on jump-up avoidance extinction with low doses (1 g/kg) increasing, and high doses (2.5 g/kg) decreasing number of trials to extinction criterion. In Experiment 1 these doses of ethanol were studied alone, and in combination with RO 15-4513 (0.3, 3 or 6 mg/kg). The stimulation of responding produced by low ethanol doses was reversed by 3 and 6 mg/kg doses of RO 15-4513 which had intrinsic suppressive effects, but the depressed responding produced by higher ethanol doses was not attenuated by RO 15-4513. Experiment 2 analysed the interaction between ethanol and benzodiazepine antagonists RO 15-1788 and CGS 8216. RO 15-1788 did not have intrinsic action and did not interact with ethanol. CGS 8216 showed an intrinsic suppressive action much like RO 15-4513, and also reversed the stimulation produced by low dose ethanol, but not the effects of the high dose. Experiment 3 showed that the benzodiazepine agonist, chlordiazepoxide, had effects much like low dose ethanol which were reversed by CGS 8216 and RO 15-4513. The major conclusions were that RO 15-4513 and CGS 8216 possess inverse agonist properties which may cancel out the effects of alcohol under certain circumstances.     

The competitive N-methyl-D-aspartate (NMDA) antagonist CGS 19755 attenuates the rate-decreasing effects of NMDA in rhesus monkeys without producing ketamine-like discriminative stimulus effects

The purported competitive excitatory amino acid antagonist CGS 19755 was compared to the non-competitive antagonists ketamine and MK-801 in three rhesus monkeys discriminating between 1.78 mg/kg of ketamine and saline while responding under a fixed-ratio 100 schedule of food presentation. MK-801 substituted completely for the ketamine discriminative stimulus and was 32 times more potent than ketamine as a discriminative stimulus. CGS 19755 was studied using single and cumulative dosing procedures up to a dose of 10.0 mg/kg; for all conditions, CGS 19755 produced responding exclusively on the saline lever and had only modest rate-decreasing effects. N-Methyl-D-aspartate administered alone also did not produce ketamine-appropriate responding but did decrease response rates in a dose-related manner. N-Methyl-D-aspartate eliminated responding in all monkeys at doses of 5.6-10.0 mg/kg. MK-801 and ketamine antagonized the rate-decreasing effects of N-methyl-D-aspartate, however, ketamine was most effective as an antagonist at doses that decreased response rates when administered alone. CGS 19755 also attenuated the rate-decreasing effects of N-methyl-D-aspartate and shifted the N-methyl-D-aspartate dose-effect curve more than 5-fold to the right. The magnitude of antagonism of N-methyl-D-aspartate appeared to be somewhat greater with CGS 19755 than with MK-801 or ketamine. Thus, a competitive (CGS 19755) and some non-competitive (MK-801 and ketamine) excitatory amino acid antagonists can attenuate the rate-decreasing effects of N-methyl-D-aspartate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antagonism by CGS 8216 and Ro 15-1788, benzodiazepines antagonists, of the action of chlordiazepoxide on a timing behavior in rats

Rats were trained to respond under a differential reinforcement of low rate (DRL) schedule of reinforcement. Pretreatment with relatively low doses of chlordiazepoxide (1-10 mg/kg) produced increases in total DRL responses and decreases in the numbers of reinforced responses. Chlordiazepoxide produced a shift in the interresponse time (IRT) distribution of DRL responses. Low doses of chlordiazepoxide shifted the IRT distribution of DRL responses. Low doses of chlordiazepoxide shifted the IRT distribution from the reinforced to the non-reinforced bins. In addition there was marked increase in the number of responses that occurred in the earliest IRT bin (0-3.75 sec). The highest dose of chlordiazepoxide (32 mg/kg) produced a decrease in total DRL responses and resulted in an even IRT distribution of responses. Both CGS 8216 and Ro 15-1788 had minimal effect on DRL responding when given alone. Ro 15-1788 had no effect at either 10 or 32 mg/kg, while CGS 8216 produced decreases in DRL responding at 32 and 100 mg/kg. Both Ro 15-1788 and CGS 8216 antagonized the effects of high and low chlordiazepoxide doses on total DRL responding and on the IRT distribution of responding.     

CGS 9896, a chloro-derivative of the diazepam antagonist CGS 8216, exhibits anxiolytic activity in the pentylenetetrazol-saline discrimination test

The effects of CGS 8216, a diazepam antagonist, and CGS 9896, a chloro-derivative of CGS 8216, were assessed in an animal model of anxiety: discrimination of interoceptive discriminable stimuli (IDS) induced by pentylenetetrazol (PTZ). Rats were trained to discriminate the effects of an anxiogenic drug, PTZ, from those of saline by pressing one of two levers in an operant chamber. When given saline followed by PTZ (20 mg/kg), all subjects reliably selected the PTZ-appropriate lever. When either diazepam or CGS 9896 (5, 20, or 80 mg/kg) injection preceded PTZ treatment, fewer subjects selected the PTZ-appropriate lever. When given before either diazepam or CGS 9896, however, CGS 8216 (40 mg/kg) reversed their blockade of PTZ-appropriate lever selection. These findings support the characterization of CGS 8216 as an effective diazepam antagonist, in vivo, with respect to an anxiolytic effect. CGS 9896 was effective in blocking the PTZ-induced IDS, establishing anxiolytic action in this animal model of anxiety.     

Ethanol suppression of schedule-controlled responding: interactions with Ro 15-4513, Ro 15-1788 and CGS 8216

Rats (N = 14) were trained to respond under a five seconds differential reinforcement of low rate (DRL 5') schedule and under a fixed ratio 10 (FR10) schedule of reinforcement. Ro 15-1788 did not influence the number of responses in the DRL 5' schedule, but increased responding in the FR10 schedule. Ethanol (ETOH, 1250 mg/kg) and CGS 8216 (5 mg/kg) suppressed responding in both schedules and these effects were not antagonized by Ro 15-1788. The response suppressing effects of ETOH in both schedules were not influenced by CGS 8216. These results indicate that the response suppressing effects of ETOH and CGS 8216 are not mediated by the BDZ receptor. Ro 15-4513 suppressed responding strongly in the FR10 schedule. The response suppressing effects of Ro 15-4513 were additive with the response suppressing effects of ETOH. In rats (N = 11) trained to respond under a variable interval 40 seconds-fixed ratio 10 (VI 40'-FR10) schedule Ro 15-4513 dose-dependently suppressed responding. These results indicate that Ro 15-4513 has sedative effects and is not able to antagonize all the behavioral actions of ETOH.     

Generalization of behavioral history across responses in the reversal of the effects of cocaine and d-amphetamine on the punished behavior of squirrel monkeys

Previous research has demonstrated that the effects of d-amphetamine on punished lever pressing of squirrel monkeys are modified by an avoidance history in which lever pressing postpones shock. In the present experiment generalization of behavioral history across responses was assessed by determining the effects of d-amphetamine and cocaine on punished lever pressing of squirrel monkeys before and after exposure to an avoidance procedure in which a chain-pulling response postponed shock. The punishment schedule consisted of a fixed-interval 5-min schedule of food delivery in which every 30 lever presses produced a 5-mA electric shock. During avoidance sessions each chain pull postponed shock delivery for 25s; in the absence of chain pulling, shocks occurred every 5s. Only a single response manipulandum was present in each phase. Punished lever pressing was initially unaltered or decreased by d-amphetamine and cocaine. Following the chain-pull avoidance history, however, d-amphetamine produced dose-dependent increases in the punished lever pressing of all three monkeys at several doses that formerly did not alter or reduce responding; a similar pattern of results was obtained when cocaine was administered to two of the subjects. The effects of d-amphetamine and cocaine on punished lever pressing were subsequently determined within the context of a multiple schedule of lever-press punishment and chain-pull avoidance, with both manipulanda present simultaneously. The effects of the drugs on punished lever pressing within the multiple schedule were similar to their initial, pre-avoidance effects for the two monkeys whose responding was increased by both drugs in the preceding, post-avoidance phase. Chain pulling during the punishment component was dose-dependently increased, suggesting that chain pulling during punishment reduced the opportunity to exhibit increases in punishing lever pressing. The remaining monkey's punished lever pressing was increased by both drugs within the context of the multiple schedule. This experiment demonstrates that avoidance-dependent upward shifts in the dose-response curves of d-amphetamine and cocaine can occur when the punishment and avoidance responses differ, and that original effects can be partially restored when both responses are available simultaneously. The results suggest that generalization across responses of the effects of a critical behavioral history may be a general property of behavioral history phenomena within behavioral pharmacology. These findings underscore the generality and importance of behavioral history as a modulatory influence on the effects of abused drugs.     

The benzodiazepine antagonist CGS 8216 decreases both shocked and unshocked drinking in rats

Previous studies of the benzodiazepine antagonist CGS 8216 have reported that this compound may enhance the punishment-induced suppression of behaviour. In order to investigate this phenomenon further, water-deprived rats were trained to drink from a water spout during a multiple schedule with shocked and unshocked components. During the shocked components a very mild electric footshock was presented after every 20th lick. The shock slightly reduced the rate of licking during these components below that which occurred during periods without shock, although this effect decreased during the experiment. CGS 8216 (0.3–10 mg/kg) produced a dose-related reduction in licking during both schedule components. The overall volumes of water consumed were reduced by CGS 8216 as was the number of licks during the first, unshocked schedule component, before shock was applied, showing that the effect on unshocked licking was not due to a generalisation of suppression between periods with or without shock. In contrast to CGS 8216, a dose of 10 mg/kg pentylenetetrazol selectively reduced shocked licking. In a second group of rats which drank under identical conditions but without shock, CGS 8216 again reduced water intake. These results show that CGS 8216 can reduce water intake in rats regardless of whether drinking results in shock presentation.     

Antipsychotic drug effects on the behavior of squirrel monkeys differentially controlled by noxious stimuli

The effects of several antipsychotic compounds were examined on two types of behavioral performances of squirrel monkeys. Both behaviors occurred simultaneously and were maintained separately by different schedules using noxious stimuli. Steady rates of responding were maintained when a chain pulling response postponed electric shock delivery (avoidance schedule). Concurrently, positively accelerated rates of responding were maintained on a lever where the first response after 3 min produced electric shock (fixed-interval 3-min schedule). The effects of the different drugs depended both upon whether the behavior postponed or presented shock and on the particular drug. Chlorpromazine (0.001–0.03 mg/kg), haloperidol (0.001–0.01 mg/kg), molindone (0.001–0.03 mg/kg) and thiothixene (0.001–0.03 mg/kg) increased slightly or had no effect on responding under the shock-postponement schedule at doses that decreased responding maintained by shock presentation. The effects of clozapine, a clinically effective antipsychotic compound, differed markedly from the other antipsychotic drugs. Clozapine (0.01–1.0 mg/kg) increased responding maintained by the presentation of shock at doses that decreased responding under the shock-postponement schedule. Higher doses of these drugs decreased responding under both schedules and, with the exception of clozapine, resulted in increased frequency of shocks under the postponement schedule.     

The adenosine receptor antagonist CGS15943 reinstates cocaine-seeking behavior and maintains self-administration in baboons

Rationale Caffeine and the adenosine A₁ and A_2A receptor antagonist CGS15943 produce many behavioral effects that are similar to those produced by classic stimulant drugs (e.g. cocaine and amphetamines). Objectives The current study evaluated whether CGS15943 would maintain self-administration and reinstate extinguished lever responding previously maintained by cocaine (i.e. cocaine-seeking) or by food (i.e. food-seeking). Reinstatement with CGS15943 was compared to cocaine, caffeine, and alprazolam. Methods Up to 30 injections of 0.032 mg/kg cocaine or 30 deliveries of 1-g food pellets were available under a fixed ratio (FR10) schedule of reinforcement during daily 2-h sessions. For reinstatement tests, lever responses were extinguished by substituting saline for cocaine or by removing pellets from the mechanical feeder. After extinction of lever responding, acute "priming" doses (mg/kg, IV) of cocaine (0.1–3.2), the adenosine receptor antagonists caffeine (0.1–1.8) and CGS15943 (0.032–0.32) or the benzodiazepine receptor agonist alprazolam (0.1–1.8 mg/kg) were administered. The intravenous reinforcing effects of CGS15943 were also evaluated; each dose of CGS15943 (0.001–0.032 mg/kg) was substituted for cocaine for at least 10 days and until self-injection was relatively stable. Results Cocaine, caffeine and CGS15943, dose-dependently increased cocaine-seeking, where as alprazolam did not. Cocaine, caffeine and CGS15943 did not increase food-seeking. CGS15943 reinstated cocaine-seeking at rates that were comparable to those produced by cocaine. Pretreatment with the adenosine A₂ agonist CGS21680 decreased CGS15943-induced reinstatement of cocaine-seeking. In self-injection testing, CGS15943 was self-administered at levels greater than vehicle. An inverted U-shaped dose-effect function was obtained with peak mean rates maintained by 0.01 mg/kg CGS15943. Conclusions The adenosine antagonist CGS15943 reinstated cocaine-seeking and functioned as an intravenous reinforcer. The finding that CGS21680 produced a rightward shift in the CGS15943 reinstatement dose-effect curve supports a role of adenosine mechanisms in the reinstatement of cocaine-seeking behavior.     

Long-term chlorpromazine in rhesus monkeys: Production of dyskinesias and changes in social behavior

Squirrel monkeys responded under a multiple schedule in which 30 responses during a specified time limit resulted in either food presentation or termination of visual stimuli associated with impending shock delivery. Schedule components were associated with different colored lights and were separated by 60-s timeout periods in which all lights were extinguished. If the response requirement was not met within the time limit, either the time-out period alone (food components) was presented or a single shock was delivered coincident with onset of time-out. In experiments with d-amphetamine, different control rates of responding were engendered by varying the time limit. When the time limit was 60 s, all monkeys responded at higher overall rates during food presentation components. When the time limit was reduced to 15s, rates of responding in both components increased and became more similar than under the 60-s limit. When control rates in the two components differed under the 60-s time limit, d-amphetamine sulfate (0.01–1.0 mg/kg) increased the normally lower rates under the shock schedule at intermediate doses, but generally only decreased the higher rates under the food schedule. With more comparable control rates under the 15-s time limit, the effects of amphetamine were also more comparable. In most cases low and moderate doses either had little effect or slightly increased responding in both schedule components and higher doses decreased responding. Morphine sulfate (0.03–1.7 mg/kg) and clozapine (0.1 – 3.0 mg/kg) decreased responding comparably under both food and shock schedules with the 15-s time limit.     

Effects of d-amphetamine and ethanol alone and in combination on schedule-controlled responding of pigeons

Key pecking by pigeons was maintained under either a 5-min fixed-interval or a 30-response fixed-ratio schedule of food delivery. d-Amphetamine (0.1–1.0 mg/kg) either increased or did not affect overall rates of responding under the fixed-interval schedule; the lowest dose of ethanol (0.5 g/kg) did not affect or slightly decreased response rates, whereas higher doses (1.0–2.0 g/kg) substantially decreased rates. Combinations of low noneffective ethanol doses with most doses of d-amphetamine increased rates of responding under the fixed-interval schedule above those obtained with d-amphetamine alone; decreases produced by the higher doses of ethanol were attenuated by most doses of d-amphetamine. Doses of d-amphetamine (0.1–1.0 mg/kg) and ethanol (0.5–1.5 g/kg) alone generally had no effect on responding maintained under the fixed-ratio schedule; higher doses of these drugs decreased responding. The effects of dose combinations other than the highest ones generally differed little from those obtained with ethanol alone; the effects of high doses of each drug were antagonized by low to moderate doses of the other. Combinations of ethanol with d-amphetamine can result in higher rates of responding than are obtained with either drug alone. Further, effects of the drugs alone and in combination depend on the schedule under which behavior is maintained.     

Lorazepam and pentobarbital discrimination: interactions with CGS 8216 and caffeine

Baboons and rats were trained under a two-lever, food-reinforced drug discrimination procedure. The training drug was either lorazepam (1.0 mg/kg) or pentobarbital (5.6 mg/kg in baboons, 10.0 mg/kg in rats). Under test conditions, a range of training drug doses occasioned 100% drug lever responding. CGS 8216 (3.2-10.0 mg/kg) combined with lorazepam produced a complete shift to the no-drug lever in both species; this shift was surmountable with higher doses of lorazepam. CGS 8216 (32.0 mg/kg) combined with pentobarbital produced a statistically significant decrease in drug-lever responding in rats, and in baboons CGS 8216 initially, but not subsequently, produced a complete shift to the no-drug lever. Caffeine (0.32-10.0 mg/kg) combined with lorazepam inconsistently decreased drug-lever responding across multiple determinations in baboons and significantly decreased drug lever responding in rats. Caffeine combined with pentobarbital also yielded an inconsistent decrease in drug lever responding in baboons but there was no effect in rats. Thus the most reliable and complete antagonism across species was obtained with the CGS 8216/lorazepam combinations.     

Increased sensitivity to benzodiazepine antagonists in rats following chronic treatment with a low dose of diazepam

The effects of benzodiazepine (BZ) antagonists on operant behavior were examined in rats chronically administered a low dose of diazepam (DZ). The low maintenance dose of DZ (5 mg/kg twice daily) was selected as more closely associated with its anxiolytic effects than the higher treatment doses previously used to study BZ dependence. Food-restricted rats were trained to press a lever for food reinforcement under a FR20 schedule of reinforcement prior to the start of DZ administration. Acute administration of DZ caused a dose-dependent reduction of response rates, with 5 mg/kg causing a 50% decrease. Rats treated chronically with DZ became tolerant to its rate-suppressant effects as shown by a 5-fold increase in the dose of DZ required to reduce FR20 response rates by 50%. The BZ antagonist flumazenil (formerly Ro 15-1788; 10–56 mg/kg) suppressed rates of responding in rats treated chronically with DZ. The suppression of operant responding was obtained when flumazenil was given up to 3 h, but not 18 h, after the last treatment with DZ. In contrast, only the highest dose of flumazenil (56 mg/kg) caused reductions of operant responding when given to rats treated with saline. The BZ antagonist CGS 8216 (3.3–33 mg/kg IP), given 10 min prior to the session, was similarly more potent and effective at suppressing operant responding in rats treated chronically with DZ than saline. This procedure may provide a model for the clinical problem of physical dependence to chronically-administered low, anxiolytic doses of BZ tranquilizers.     

Ethanol decreases responding on behavior maintained under concurrent schedules of both positive reinforcer presentation and avoidance in humans

Six human volunteers were tested during 15min sessions under the behavioral contingencies of a concurrent fixed-ratio, fixed-ratio schedule of point-gain reinforcement and point-loss avoidance. Completion of each fixed-ratio 50 (FR 50) on the point-gain lever produced 10 points, which were exchanged for money ($.01 per point) after each week of the study. Point losses of 10 points were scheduled to occur during the session on a variable-time 60sec schedule. The total amount of money accumulated was continuously displayed on video monitor. Subjects were exposed to the concurrent schedule until responding under the schedules of point gain and point loss stabilized. After responding had stabilized under these contingencies (4-5 sessions), subjects were tested each day 30min following administration of ethanol, in doses of 0.32, 0.64 or 0.96g/kg, or placebo. Ethanol decreased responding in all subjects and produced dose-related decreases in overall response rates in three subjects. These effects were not related to self-reported current alcohol consumption. Response rates on the reinforcement and the avoidance schedules were both decreased by ethanol. Thus, under these conditions, behavioral effects of ethanol on concurrent FR responding did not depend on the nature of the consequent event.