Chronic morphine consumption decreases wheel running and wheel running-reinforced behavior in rats.

The purpose of this experiment was to evaluate the effects of morphine self-administration on wheel running and wheel running-reinforced lever pressing in rats. The home cage was equipped with a bottle that contained either water, a saccharin-flavored 0.5-mg/ml morphine solution, or saccharin (0.25%). The bottle was available for either 1 or 3 h. The bottle was then removed, and 20-22 h after removal, the rats were moved to an operant chamber in which lever presses earned 15 s access to a running wheel (according to a variable interval (VI) 40-s schedule). The morphine condition was in effect for 69 days, and consumption gradually increased to a level of 67 mg/kg/day. During the morphine condition, wheel running and lever pressing decreased. Following the removal of morphine, (so that the home-cage bottles provided a 0.25% saccharin solution), the two instrumental behaviors increased to the pre-morphine (water) levels. However, the increases were not immediate, and in the first post-morphine session, lever pressing and wheel turning remained at the depressed morphine level. The post-morphine increase in lever pressing was substantially larger than the increase in wheel running. The results support the hypothesis that chronic opiate consumption reduces the frequency of some nondrug-related behaviors, and that this, in turn, increases preference for the opiate.

A comparison of the reinforcing efficacy of alcohol in alcohol-preferring (P) and alcohol-nonpreferring (NP) rats.

A key feature of the selective breeding program that produced alcohol-preferring (P) and alcohol-nonpreferring (NP) rats is that the alcohol was mixed with water. However, humans typically drink sweetened or palatably flavored alcohol. The experiments in this study tested whether the differences in P and NP rats generalize to sweetened alcohol. In Experiment 1, P rats drank more alcohol than NP rats when the vehicle was water, but NP rats drank about as much alcohol as P rats (1.1 to 1.3 g/kg/30 min) when the vehicle was a saccharin solution. Experiment 2 tested whether P rats were more susceptible to the rewarding properties of sweetened alcohol than were NP rats. The criterion for reward strength was the degree to which alcohol-reinforced lever pressing persisted, despite increases in the schedule requirements for the alcohol reward. In baseline, lever presses were reinforced with sweetened alcohol and an isocaloric Polycose solution according to two, concurrent, variable-interval 5-s schedules. In subsequent conditions, the interval schedule for alcohol was increased, and then, after a return to baseline, the interval schedule for Polycose was increased. By the criterion of resistance to change, alcohol was a stronger reinforcer than was Polycose, and alcohol was a stronger reinforcer in NP rats than in P rats.

An economic approach to animal models of alcoholism.

Researchers have long sought an animal model for human alcohol consumption. This article describes an economic-based approach to a model of alcohol preference in rats. The procedures are based on an analogy between clinical accounts of human drinking and the economic analysis of consumption. Both clinical and economic investigators typically define consumption patterns in terms of the influence of negative consequences. For example, the clinical account emphasizes the persistence of heavy drinking despite mounting alcohol-related aversive consequences, and in economic analyses, the term "inelastic demand" is used to refer to the persistence of consumption despite large increases in prices. In the experimental procedure described here, rats worked for alcohol and food. Presses on one lever earned a drink of 10 percent alcohol plus saccharin, and presses on a second lever earned isocaloric drinks of a starch solution. After behavior stabilized, the response requirements (which are analogous to prices) for one or both drinks were increased. The rats maintained baseline alcohol consumption levels despite large increases in the "price" of alcohol. In contrast, the same price increases markedly reduced starch intake. That is, food consumption was sensitive to price hikes, but alcohol consumption was not. The results demonstrate that a common economic framework can be used to describe human and animal behavior and, hence, the possibility of an animal model of human alcohol consumption. The article also points out that economic concepts provide a framework for understanding a wide range of human drinking patterns, including controlled social drinking and excessive alcoholic drinking.

Inelastic demand for alcohol in rats.

RATIONALE: For the purpose of investigating the determinants of preference for alcohol, it would be advantageous to use a procedure in which the subjects had concurrent access to alcohol and an isocaloric food. However, in widely used animal models, the introduction of a weak sucrose solution markedly reduced alcohol consumption. In contrast, when alcohol was sweetened, rats defended high baseline levels of alcohol intake despite access to chow, 10% sucrose, and increases in body weight that markedly reduced food consumption. Under these conditions, certain pharmacological treatments selectively reduced alcohol consumption. The present experiment further tests the generality of the contrast between food and sweetened alcohol consumption in rats. OBJECTIVE: To test if rats will defend baseline levels of alcohol consumption when (1) the competing reinforcer is an isocaloric, preferred food and (2) when the cost of defending alcohol entails a decrease in food consumption as well as an increase in response output. METHODS: The rats had access to a 10% alcohol plus 0.25% saccharin solution and an isocaloric, 14.8% Polycose solution in a two-lever, choice procedure. In the initial condition, the response requirement for each drink was set at five responses (variable-ratio 5); in subsequent conditions the variable-ratio values were increased to 7.5, 10, 15, and 30 responses. RESULTS: In the initial condition, the rats drank twice as much Polycose as alcohol. However, with increases in the variable-ratio requirements, Polycose consumption systematically decreased, whereas sweetened alcohol consumption remained at its baseline level or above in all but the variable-ratio 30 condition. CONCLUSIONS: Rats defended baseline alcohol consumption but not baseline food consumption. As alcohol and food consumption can be dissociated in humans, research on the mechanisms that mediate alcohol regulated preference in rats may shed light on the mechanisms that control human alcohol consumption.

Bidirectional modulation of sweet and bitter taste by chlordiazepoxide and Ro 15-4513: lack of effect with GABA drugs.

Five rats were trained to respond for 10% sucrose and 10% sucrose/0.006% quinine in an operant procedure. Both solutions were concurrently available on independent, variable-interval 5-s schedules of reinforcement. Rats reliably responded for both solutions throughout the sessions and made approximately 68% of their total daily responses for the sucrose solution. When injected prior to the sessions with 4 mg/kg of chlordiazepoxide, rats selectively increased quinine responding; injections of the benzodiazepine inverse agonist Ro 15-4513 (9 mg/kg) led to decreased quinine responding. The effects of both chlordiazepoxide and Ro 15-4513 were reversed by the benzodiazepine antagonist flumazenil. Presession injections of flumazenil, muscimol, baclofen, or picrotoxin all resulted in no changes in responding, or a decrease in responding for both solutions. These results are discussed in terms of a bidirectional modulation of sweet-bitter taste preference by drugs acting on the benzodiazepine receptor. Moreover, the data from these experiments suggest that any changes in the oral consumption of alcohol following administration of benzodiazepine drugs must be examined in light of their effects on taste palatability.

Preference for saccharin-sweetened alcohol relative to isocaloric sucrose.

This experiment tested the reinforcing efficacy of a saccharin-sweetened alcohol solution relative to an isocaloric sucrose drink in rats. One dipper served 10% alcohol plus 0.25% saccharin, and a second, concurrently available, dipper served 14.2% sucrose. During the course of the experiment, access to the two drinks was challenged by increasing the schedule requirement (variable-interval) that determined when a lever press would operate the dipper. There were two main findings. First, the rats continued to consume significant amounts of alcohol despite access to the isocaloric sucrose solution. Second, schedule-requirement increases that decreased sucrose-reinforced responding failed to decrease saccharin-sweetened alcohol reinforced responding. These results extend and replicate earlier findings from studies in which alcohol was mixed with sucrose, and the alcohol mixtures held a caloric advantage over the competing sucrose solutions. The experiment also included controls for differences in baseline response rates and for the influence of saccharin on preference. In the baseline response-rate control conditions, the two reinforcers were 10% sucrose and a mixture of 10% sucrose-plus-quinine. The results showed that the persistence of sweetened-alcohol reinforced responding could not be explained by differences in baseline response rates or the reinforcing properties of saccharin. Rather, the findings were consistent with the idea that the rats were defending baseline levels of alcohol-plus-saccharin consumption.

Rat toys, reinforcers, and response strength: An examination of the Re parameter in Herrnstein's equation.

The response-strength equation is a mathematical model used to explain responding on variable-interval (VI) schedules. This equation has two fitted parameters, k and Re. Empirical research suggests that k is a measure of motor performance and Re is a measure of background sources of reinforcement relative to the arranged reinforcer. This experiment examined the interpretation of the Re parameter by augmenting the background reinforcement with a qualitatively different source of background reinforcement. Rats were food deprived and received sucrose solution for lever responding. Each experimental session consisted of a series of seven VI schedules, providing reinforcement rates that varied between 20 to 1200 h(-1). Occasionally, cardboard tubes were introduced into the experimental chambers in order to provide the rats with another source of reinforcement distinct from the lever-response specific sucrose reinforcer. The k parameter did not change systematically as a result of the experimental manipulations, but Re was significantly larger when tubes were introduced into the chambers. These results are consistent with the interpretation that k and Re measure two independent and experimentally distinguishable parameters and that Re is a measure of reinforcement of background sources to the arranged reinforcer.

Daidzin decreases ethanol consumption in rats.

In a previous study, daidzin, a constituent of an ancient Chinese herbal treatment for alcoholism, decreased home-cage ethanol consumption in laboratory Syrian golden hamsters. The present study tested the generality of daidzin's antidipsotropic effects. Rats served as subjects in a two-lever choice procedure. At one lever, responses earned 10% ethanol, flavored with saccharin. At the other lever, responses earned an isocaloric starch solution. Daidzin decreased both ethanol and starch consumption, but the decreases in ethanol intake were larger. Changes in consumption were dose dependent, and differences in ethanol and food consumption increased slightly (but significantly) as dose increased. Daidzin produced a similar pattern of decreases in lever pressing. In baseline, there was an approximately equal distribution of responses between the two levers; at the highest daidzin dose, the relative number of responses at the ethanol lever decreased to 30%. These results replicate and extend earlier findings, and they encourage further research on daidzin's capacity to decrease ethanol consumption.

How to teach a pigeon to maximize overall reinforcement rate.

In two experiments deviations from matching earned higher overall reinforcement rates than did matching. In Experiment 1 response proportions were calculated over a 360-response moving average, updated with each response. Response proportions that differed from the nominal reinforcement proportions, by a criterion that was gradually increased, were eligible for reinforcement. Response proportions that did not differ from matching were not eligible for reinforcement. When the deviation requirement was relatively small, the contingency proved to be effective. However, there was a limit as to how far response proportions could be pushed from matching. Consequently, when the deviation requirement was large, overall reinforcement rate decreased and pecking was eventually extinguished. In Experiment 2 a discriminative stimulus was added to the procedure. The houselight was correlated with the relationship between response proportions and the nominal (programmed) reinforcement proportions. When the difference between response and reinforcement proportions met the deviation requirement, the light was white and responses were eligible for reinforcement. When the difference between response and reinforcement proportions failed to exceed the deviation requirement, the light was blue and responses were not eligible for reinforcement. With the addition of the light, it proved to be possible to shape deviations from matching without any apparent limit. Thus, in Experiment 2 overall reinforcement rate predicted choice proportions and relative reinforcement rate did not. In contrast, in previous experiments on the relationship between matching and overall reinforcement maximization, relative reinforcement rate was usually the better predictor of responding. The results show that whether overall or relative reinforcement rate better predicts choice proportions may in part be determined by stimulus conditions.

Behavioral economics of concurrent ethanol-sucrose and sucrose reinforcement in the rat: effects of altering variable-ratio requirements.

These experiments examined the own-price and cross-price elasticities of a drug (ethanol mixed with 10% sucrose) and a nondrug (10% sucrose) reinforcer. Rats were presented with ethanol-sucrose and sucrose, both available on concurrent independent variable-ratio (VR) 8 schedules of reinforcement. In Experiment 1, the variable ratio for the ethanol mix was systematically raised to 10, 12, 14, 16, 20, and 30, while the variable ratio for sucrose remained at 8. Five of the 6 rats increased ethanol-reinforced responding at some of the increments and defended baseline levels of ethanol intake. However, the rats eventually ceased ethanol-reinforced responding at the highest variable ratios. Sucrose-reinforced responding was not systematically affected by the changes in variable ratio for ethanol mix. In Experiment 2, the variable ratio for sucrose was systematically increased while the ethanol-sucrose response requirement remained constant. The rats decreased sucrose-reinforced responding and increased ethanol-sucrose-reinforced responding, resulting in a two- to 10-fold increase in ethanol intake. Experiment 3 examined the substitutability of qualitatively identical reinforcers: 10% sucrose versus 10% sucrose. Increases in variable-ratio requirements at the preferred lever resulted in a switch in lever preference. Experiment 4 examined whether 10% ethanol mix substituted for 5% ethanol mix, with increasing variable-ratio requirements of the 5% ethanol. All rats eventually responded predominantly for the 10% ethanol mix, but total amount of ethanol consumed per session did not systematically change. In Experiment 5, the variable-ratio requirements for both ethanol and sucrose were simultaneously raised to VR 120; 7 of 8 rats increased ethanol-reinforced responding while decreasing sucrose-reinforced responding. These data suggest that, within this ethanol-induction procedure and within certain parameters, demand for ethanol-sucrose was relatively inelastic, and sucrose consumption was independent of ethanol-sucrose consumption. Demand for sucrose, on the other hand, was relatively elastic, and ethanol-sucrose readily substituted for it. The results are discussed in terms of applying a behavioral economic approach to relationships between drug and nondrug reinforcers.

Reinforcer magnitude (sucrose concentration) and the matching law theory of response strength.

This experiment investigated the relationship between reinforcer magnitude (sucrose concentration) and response rate. The purpose was to evaluate the behavior of two parameters of an equation that predicts absolute response rate as a function of reinforcement rate and two free parameters. According to Herrnstein's (1970) theory of reinforced behavior, one parameter of this "response-strength equation" measures the efficacy of the reinforcer maintaining responding and the other parameter measures motoric components of response rate, such as response duration. Seven rats served as subjects. Experimental sessions consisted of a series of five different variable-interval schedules of reinforcement, each in effect for 5 minutes. Within each session, obtained reinforcement rates varied over more than a 30-fold range, from about 20 per hour to 700 per hour. The reinforcer was sucrose solution, and, between sessions, its concentration was varied from 0.0 to 0.64 molar (0 to 21.9%). For sucrose concentrations of 0.16 to 0.64 m, response rate was a negatively accelerated function of reinforcement rate. Increases in sucrose concentration increased response rates maintained by low but not high reinforcement rates. This pattern of changes corresponds to a change in the reinforcement-efficacy parameter of the response-strength equation. In contrast, the motor-performance parameter did not change as a function of sucrose concentration. These findings are inconsistent with the results of a similar study (Bradshaw, Szabadi, & Bevan, 1978) but support Herrnstein's theory of reinforced behavior.

Increasing and signaling background reinforcement: effect on the foreground response-reinforcer relation.

Herrnstein's (1970) hyperbolic matching equation describes the relationship between response rate and reinforcement rate. It has two estimated parameters, k and Re. According to one interpretation, k measures motor performance and Re measures the efficacy of the reinforcer maintaining responding relative to background sources of reinforcement. Experiment 1 tested this interpretation of the Re parameter by observing the effect of adding and removing an additional source of reinforcement to the context. Using a within-session procedure, estimates of Re were obtained from the response-reinforcer relation over a series of seven variable-interval schedules. A second, concurrently available variable-interval schedule of reinforcement was added and then removed from the context. Results showed that when the alternative was added to the context, the value of Re increased by 107 reinforcers per hour; this approximated the 91 reinforcers per hour obtained from this schedule. Experiment 2 investigated the effects of signaling background reinforcement on k and Re. The signal decreased Re, but did not have a systematic effect on k. In general, the results supported Herrnstein's interpretation that in settings with one experimenter-controlled reinforcement source, Re indexes the strength of the reinforcer maintaining responding relative to uncontrolled background sources of reinforcement.

Effects of qualitatively different reinforcers on the parameters of the response-strength equation.

This experiment examined the relationship between two qualitatively different reinforcers and the parameters of a quantitative model of reinforced responding, referred to as the response-strength equation or the Herrnstein equation. A group of rats was first food deprived and later water deprived. An 11.5% sucrose solution served as the reinforcer in the food-deprivation condition, and water was the reinforcer in the water-deprivation condition. Each experimental session consisted of a series of seven variable-interval schedules, providing reinforcement rates that varied between 20 and 1,200 reinforcers per hour. The response rates increased in a negatively accelerating function in a manner consistent with the response-strength equation. This equation has two fitted parameters, k and Re. According to one theory, the k parameter is a measure of motor performance, and Re is indicative of the relative reinforcement efficacy of the background uncontrollable sources of reinforcement in relation to the experimentally arranged reinforcer. In this study, k did not change as a result of the different reinforcers, but Re was significantly larger in the sucrose-reinforcement condition. These results are consistent with the interpretation that k and Re measure two independent and experimentally distinguishable parameters and provide further evidence that absolute response rate is a function of relative reinforcement rate, as implied by the derivation of the response-strength equation based on the matching law.

Ethanol regulated preference in rats.

A series of experiments evaluated the determinants of preference for mixtures of ethanol plus sucrose relative to sucrose in rats. One dipper served 10% ethanol mixed with 10% sucrose, and the second dipper served 10% sucrose. Lever presses operated each dipper according to a variable-interval 5-s schedule. In three experiments the subjects were given pre-session meals of sucrose (2.5-20 ml) or sucrose (20 ml) plus chow (5 or 10 g). Pre-session meals decreased responding maintained by sucrose but not responding maintained by ethanol mixture. In two experiments body weight was varied from 85% to 125% of the initial free-feeding values. Increases in body weight, like pre-session meals, decreased responding reinforced by sucrose, but typically did not decrease responding reinforced by ethanol mixture. Throughout most of the study, ethanol consumption remained at about 1.25 ml per half hour session (3-4 g/kg per 30 min). For example, pre-session access to ethanol mixture decreased within-session ethanol consumption, but total consumption, counting both sources, remained about 1.25 ml/session. The within-session patterns of responding also differed. Responding reinforced by ethanol mix decreased as a function of ethanol consumption, whereas responding reinforced by sucrose was relatively constant throughout the session. The simplest explanation of the results is that ethanol's pharmacological consequences regulated preference.

Effects of methylphenidate on response rate and measures of motor performance and reinforcement efficacy.

This experiment evaluated the effects of methylphenidate on reinforced responding in rats. In each session the subjects (rats) earned reinforcement on seven different variable-interval reinforcement schedules. The average intervals varied from 108 to 3 s and provided reinforcement rates ranging from about 30 to 1100/h. Response rate was a negatively accelerated function of reinforcement rate. Low doses of methylphenidate (1.0 and 2.0 mg/kg) increased responding maintained by the four leanest schedules, but had little effect on responding maintained by the three densest schedules. In contrast, an 8.0 mg/kg dose increased responding maintained by the three densest schedules and slightly decreased responding maintained by leaner schedules. A quantitative model of reinforced responding, referred to as the matching law or response strength equation, was fitted to the data. This equation has two parameters. On the basis of previous experiments, one was used to measure changes in reinforcement efficacy and the other was used to measure changes in motor performance. The 1.0 and 2.0 mg/kg doses changed the reinforcement parameter in the same way as did increases in deprivation and reward magnitude. The 8.0 mg/kg dose changed the motor parameter in the same was as did decreases in lever weight. It was concluded that methylphenidate increases reinforcement efficacy, and that the highest dose changed the topography of responding. The results are discussed in terms of the response strength equation, the rate dependency principle, and the question of how to interpret changes in reinforcement efficacy and motor performance.

Low doses of cis-flupentixol attenuate motor performance.

We evaluated the effects of cis-flupentixol on reinforced responding. The experimental subjects were rats and the reinforced response was a lever press. The procedure was a five-component multiple schedule that provided five different reinforcement rates. Cis-flupentixol produced dose-dependent decreases in reinforced responding. An equation, the matching law, was fitted to the results. One parameter of this equation represents the estimated response rate asymptote. Cis-flupentixol produced dose-dependent decreases in the asymptotes. A second parameter of the equation represents the rate of reinforcement that maintains a one-half asymptotic response rate. Cis-flupentixol did not appear to affect this measure. There is evidence that the response rate asymptote measures motor components of response rate and that the reinforcement parameter measures the efficacy of the reinforcement maintaining the response. According to these results, cis-flupentixol systematically affected the motor-component of reinforced responding-it slowed down lever pressing-without affecting the subject's sensitivity to the reinforcer maintaining the response. In contrast, other neuroleptics have decreased the subjects' sensitivity to reinforcement, according to the matching law measures.

More on concurrent interval-ratio schedules: a replication and review.

It has been suggested that the failure to maximize reinforcement on concurrent variable-interval, variable-ratio schedules may be misleading. Inasmuch as response costs are not directly measured, it is possible that subjects are optimally balancing the benefits of reinforcement against the costs of responding. To evaluate this hypothesis, pigeons were tested in a procedure in which interval and ratio schedules had equal response costs. On a concurrent variable time (VT), variable ratio-time (VRT) schedule, the VT schedule runs throughout the session and the VRT schedule is controlled by responses to a changeover key that switches from one schedule to the other. Reinforcement is presented independent of response. This schedule retains the essential features of concurrent VI VR, but eliminates differential response costs for the two alternatives. It therefore also eliminates at least one significant ambiguity about the reinforcement maximizing performance. Pigeons did not maximize rate of reinforcement on this procedure. Instead, their times spent on the alternative schedules matched the relative rates of reinforcement, even when schedule parameters were such that matching earned the lowest possible overall rate of reinforcement. It was further shown that the observed matching was not a procedural artifact arising from the constraints built into the schedule.

Chlorpromazine and pimozide alter reinforcement efficacy and motor performance.

This study evaluated the effects of chlorpromazine and pimozide on reinforced responding. In each session, rats were exposed to a series of five variable-interval reinforcement schedules. The response requirement was a lever press, the reward was a small portion of water, and the reinforcement rate varied from about 20 to 660 reinforcers per hour. Response rate was a negatively accelerated function of reinforcement rate, and the relationship between the two variables was described by the equation for a rectangular hyperbola (the matching law). One parameter of the hyperbola is equivalent to the asymptotic response rate and the other parameter is equivalent to the rate of reinforcement that maintains a one-half asymptotic response rate. Chlorpromazine (0.75-3.0 mg/kg) and pimozide (0.1-0.4 mg/kg) dose-dependently decreased response rates. At low doses, the response rate decreases were, for the most part, restricted to the low reinforcement rate schedules. In contrast, the highest dose tested decreased response rates at both low and high reinforcement rates. The patterns of response rate decreases resulted in dose-dependent changes in the parameters of the matching law equation. The shifts in the matching law parameters were discussed in terms of the motoric and motivational interpretations of neuroleptic-induced response rate changes.

A parametric description of amphetamine's effect on response rate: changes in reinforcement efficacy and response topography.

A mathematical model was used to describe the effects of amphetamine on the rate of a reinforced response in the rat. The model provides measures of reinforcement efficacy and response topography for behavior maintained by variable-interval reinforcement schedules. In this study the measured behavior was a lever press, the reinforcer was water, and the variable-interval schedules provided five different rates of reinforcement, ranging from about 20 to 660/h. In each session the rats were exposed to each of the five schedules, and as reinforcement rate increased, the rate of lever pressing increased in a negatively accelerated manner that was closely approximated by the equation for a rectangular hyperbola. Amphetamine changed response rate and the parameters of the best-fitting hyperbolas. The 0.25-1.0-mg/kg doses increased response rate, and the parameter changes supported the interpretation that the increases were due primarily to an increase in reinforcement efficacy. The 2.0- and 3.0-mg/kg doses decreased response rates maintained by low reinforcement rates and increased response rates maintained by high reinforcement rates, and the parameter changes supported the interpretation that at higher doses amphetamine produced counteracting changes in reinforcement efficacy and response topography: reinforcement efficacy decreased, whereas response topography changed so as to increase response rates.