Acquisition,Extinction, Recovery,and Reversal of Different Response Sequences Under Conditional Control by Nicotine in Rats

Complex voluntary behaviors occur in sequence. Eight rats were trained in an operant procedure that used nicotine and non-drug (saline) states as interoceptive cues that signaled which of two behavioral sequences led to food reward. The distal and proximal responses in the chain were always maintained on variable interval 30-sec and fixed ratio-1 schedules, respectively, and rate differences between the responses were used as the dependent variable. Extinction and reversal training was conducted. Distal response rates were significantly greater than proximal response rates during training, testing, extinction, and reversal learning. These data suggest that (a) nicotine can establish interoceptive control over different response sequences, and (b) extinction of one response sequence may be state-dependent. The clinical relevance of extinction of complex behavioral repertoires such as drug-seeking and drug-taking behavior that are evoked by specific interoceptive cues is addressed in regard to drug abuse treatment and relapse.     

Effects of reinforcement magnitude on spontaneous recovery.

Extinction of operant behavior has been associated with a number of undesirable effects. One such effect is the temporary reappearance of behavior after responding appears to be completely extinguished, known as spontaneous recovery. In this report, the occurrence of spontaneous recovery and its attenuation with large amounts of reinforcement were examined during the treatment of disruption.     

Drug discrimination: stimulus control during repeated testing in extinction

Rats were trained, under a two-lever drug-discrimination procedure, to respond differentially depending upon whether lorazepam (1.0 mg/kg) or no injection had been administered before the session. Responses on the appropriate lever produced a food pellet under a modified fixed-ratio (FR) 10 schedule, in which the 10 responses had to be emitted consecutively. In reinforcement tests, completing an FR 10 on either lever produced a pellet. In extinction tests, stimulus changes paired with reinforcement occurred but no pellet was delivered. Training sessions were conducted between test sessions. Each of four extinction phases consisted of six tests preceded by one stimulus (e.g., lorazepam). Repeated exposures to extinction reduced response rates for all rats, but stimulus control, as inferred from either percentage of total responses or percentage of total FR 10s on the drug-appropriate lever, remained high. The percentage of total FR 10s measure was less subject to skewing under low-rate conditions than was the percentage of total responses measure and provided an evaluation of stimulus control in terms of meeting the consecutive response contingency. These results demonstrate a level of independence between response rate and stimulus control in drug discrimination, which has positive implications for the validity of interpreting discriminative effects of novel test conditions in well-trained animals, even when overall response rates are low.     

An assessment of the role of handling cues in "spontaneous recovery" after extinction

Three experiments examined the assertion that presession handling cues that accompany training with reinforcement might account for spontaneous recovery when they reoccur following extinction. In Experiment 1, after extensive training on a variable-interval schedule, key pecking in pigeons was extinguished following either normal or distinctively different handling and transportational cues. Those cues resulted in enhanced spontaneous recovery 24 hr later when normal cues were reinstated. In Experiment 2, however, subjects tested following the normal handling cues showed no more spontaneous recovery than did subjects that spent the entire extinction-test interval in the experimental chambers and thus were tested without handling cues altogether. In Experiment 3, a group whose test for recovery began 10 min after being placed in the chambers yielded as much spontaneous recovery as did a group tested normally. Furthermore, a group for which extinction began at mid-session and for which handling therefore could not be a discriminative cue for extinction showed no more spontaneous recovery than did the other two groups. Handling cues thus contributed to spontaneous recovery only after explicit discrimination training, as provided in Experiment 1.     

Discrimination between safe and unsafe stimuli mediates the relationship between trait anxiety and return of fear

Individuals with anxiety disorders show deficits in the discrimination between a cue that predicts an aversive outcome and a safe stimulus that predicts the absence of that outcome. This impairment has been linked to increased spontaneous recovery of fear following extinction, however it is unknown if there is a link between discrimination and return of fear in a novel context (i.e. context renewal). It is also unknown if impaired discrimination mediates the relationship between trait anxiety and either spontaneous recovery or context renewal. The present study used a differential fear conditioning paradigm to examine the relationships between trait anxiety, discrimination learning, spontaneous recovery and context renewal in healthy volunteers. Fear learning was assessed using continuous ratings of US expectancy and subjective ratings of fear. Discrimination mediated the relationships between trait anxiety and both spontaneous recovery and context renewal such that elevated trait anxiety was associated with poorer discrimination, which in turn was associated with increased fear at test phases. Results are discussed in terms of the genesis and maintenance of anxiety disorders.     

Nicotine vs. Ethanol Discrimination: Extinction and Spontaneous Recovery of Responding

Studies regarding extinction and spontaneous recovery of the discriminative stimulus effects of drugs are limited. Eight rats were initially trained to discriminate nicotine (0.4 mg/kg) vs. ethanol (800 mg/kg). For four rats, itraperitaneal (IP) administrations of nicotine fifteen minutes prior to fifteen-minute training sessions served as a discriminative stimulus (SD) for predicting food-reinforced lever pressing (VI-1 min). On other sessions ethanol functioned in predicting nonreinforcement (SA). The stimulus roles of the drugs were counterbalanced for the remaining four rats. SA and SD sessions alternated quasi-randomly with two daily sessions at 1000 and 1400 hours. Discriminative control was not disrupted following ten extinction sessions under a non-drug/saline condition, but was disrupted following extinction sessions under the original training drugs. Instances of spontaneous recovery (SR) occurred throughout extinction under the drug condtions. There was no evidence for SR two weeks following extinction, but partial recovery four weeks following the final extinction phase. Contextual status (context renewal) had neither a restorative or disruptive impact on extinguished or discriminated responding, respectively. These results support and extend the limited number of other studies by demonstrating extinction and spontaneous recovery of responding discriminated by two distinct drugs. Some theoretical interpretations regarding history effects and training in the context of drug discrimination are entertained.     

Extinction, spontaneous recovery and renewal of flavor preferences based on taste-taste learning

This paper presents evidence of extinction, spontaneous recovery and renewal in a conditioned preferences paradigm based on taste-taste associations. More specifically, in three experiments rats exposed to a simultaneous compound of citric acid-saccharin solution showed a preference for the citric solution when the preference was measured with a two-bottle test (citric vs. water). Experiment 1 revealed that conditioned preferences were extinguished by repeated presentations of the citric acid solution without the saccharin. In Experiment 2, an additional test trial was introduced 21 days after the extinction treatment. Delayed testing resulted in the recovery of the extinguished preference for the citric, reflecting a spontaneous recovery effect. Experiment 3 revealed a preference renewal effect that was obtained when the extinction was conducted in a context different from that of the remaining experimental stages. The implications of these results are analyzed with attention paid to the mechanisms underlying learning of flavor preferences.     

The control of responding by sounds: unusual effect of reinforcement.

Naive rats were trained to respond on one lever in the presence of noise bursts from one speaker and on a second lever in the presence of noise bursts from a second speaker. The speakers were mounted behind the levers. When responding on the lever adjacent to the sounding speaker was reinforced, control developed within fewer than five trials. When responding on the nonadjacent lever was selectively reinforced, responding on the lever adjacent to the sounding speaker increased in probability for several sessions. Naive rats were trained to respond on the nonadjacent lever following preexposure to the sound. Responding on the lever adjacent to the sounding speaker increased in probability, showing that novelty was not responsible for the effect. Naive rats were run on automaintenance procedures in which there was no explicit pairing of sound and magazine operation, 100% pairing of sound and magazine operation, or magazine operation following 40% of sound presentations. None of the rats acquired the response of approaching and sniffing the sounding speaker, indicating that sound-magazine pairing was not responsible for the effect.     

Control of responding by the location of sound: role of binaural cues.

In auditory localization experiments, where the subject observes from a fixed position, both relative sound intensity and arrival time at the two ears determine the extent of localization performance. The present experiment investigated the role of binaural cues in a different context, the sound-position discrimination task, where the subject is free to move and interact with the sound source. The role of binaural cues was investigated in rats by producing an interaural imbalance through unilateral removal of the middle auditory ossicle (incus) prior to discrimination training. Discrete trial go-right/go-left sound-position discrimination of unilaterally incudectomised rats was then compared with that of normal rats and of rats with the incus of both sides removed. While bilateral incus removal affected binaural intensity and arrival times, the symmetry of sound input between the two ears was preserved. Percentage of correct responses and videotaped observations of sound approach and exploration showed that the unilateral rats failed to localize the sounding speaker. Rats with symmetrical binaural input (normal and bilaterally incudectomised rats) accurately discriminated sound position for the duration of the experiment. Previously reported monaural localization based upon following the intensity gradient to the sound source was not observed in the unilaterally incudectomised rats of the present experiment. It is concluded that sound-position discrimination depends upon the use of binaural cues.     

Low-dose caffeine discrimination and self-reported mood effects in normal volunteers.

A caffeine versus placebo discrimination procedure was used to determine the lowest caffeine dose that could produce discrimination and self-reported mood effects in normal volunteers. During daily sessions under double-blind conditions, caffeine-abstinent subjects orally ingested a capsule containing 178 mg caffeine or placebo. Before beginning discrimination training, the compounds were identified to subjects by letter codes. Fifteen, 30, and 45 min after capsule ingestion, subjects guessed the capsule's letter code. Correct guesses at 45 min earned money. After each session, subjects received a supplementary capsule containing caffeine or placebo to ensure that, within each phase of the study, subjects received the same daily dose of caffeine equal to the training dose. Five of the 15 subjects acquired the caffeine versus placebo discrimination within the first 20 sessions (greater than or equal to 75% correct); 6 other subjects acquired the discrimination with additional training. Nine subjects who acquired the discrimination were subsequently trained at progressively lower caffeine doses. In general, the lowest dose to produce discrimination (greater than or equal to 75% correct) was also the lowest dose to produce self-reported mood effects: 4 subjects showed discrimination and self-reported mood effects at 100 mg caffeine, 2 at 56 mg, 1 at 32 mg, and 1 at 18 mg. One of these subjects also showed self-reported mood effects at 10 mg. The present study documents discriminative stimulus and self-reported mood effects of caffeine at doses below those previously shown to affect any behavior in normal volunteers.     

Control of responding by sounds of different quality: an evolutionary analysis.

Two experiments investigated the acquisition of discriminations between two acoustic stimuli of different quality (noise bursts vs. a 2-kHz pulsed signal) when features of the everyday environment were incorporated into the experiments. In Experiment 1, rats were trained, using food, to press a lever. Throughout all sessions, 5-s trials of noise bursts (the random stimulus) were presented, after variable intertrial intervals, through a remote speaker mounted outside the experimental enclosure. The noise burst occurred randomly with respect to reinforcement of lever pressing and had no programmed relationship to the animal's behavior. When lever pressing was established, the 2-kHz signal was presented through a speaker adjacent to the response lever according to a different set of variable intertrial intervals. A response in the presence of the 2-kHz signal terminated the trial and was reinforced. The 2-kHz signal acquired control of responding within the first few trials, whereas the random stimulus exerted no control of responding. In Experiment 2, rats were trained to press the lever in the presence of the 2-kHz signal presented through the adjacent speaker on a variable intertrial interval. After 14 sessions, 5-s trials of noise bursts (random stimulus) were presented through the remote speaker on the second variable intertrial interval. The random stimulus initially elicited exploratory behavior, which then rapidly declined. Subsequently, the random stimulus exerted no or weak control of responding. The introduction of the random stimulus had no effect on responding in the presence of the adjacent stimulus. In Experiments 3 and 4 the random stimulus was presented through the adjacent speaker, and the stimulus correlated with reinforcement was presented through the remote speaker. In both experiments, there was persistent control of responding by the random stimulus and slow development of control by the stimulus correlated with reinforcement. In Experiment 5, both stimuli were presented through the adjacent speaker. There was persistent control of responding by the random stimulus.     

认知重评阻断条件化恐惧记忆的习得与表达——对恐惧反应的长程抑制作用

情绪调节是人类特有的、并能有效控制个体情绪反应的行为方式,认知重评是其中最有效的调节策略之一。恐惧记忆是参与情绪障碍形成的重要病理机制,且已习得的恐惧反应难消退、易复发。为了考察认知重评能否起到长久抑制恐惧反应的效应,本研究利用条件化恐惧范式,第一天进行条件化恐惧习得训练,并在习得后间隔24 h及31天进行恐惧记忆的表达及自发恢复测试。实验1中,随机将被试分为两组,要求其在恐惧习得过程中进行认知重评或自然感受;在实验2,同样随机将被试分为两组,但要求其在恐惧记忆表达过程中进行认知重评或自然感受。结果发现,习得阶段进行认知重评显著降低了恐惧记忆的习得、表达及自发恢复过程中的SCR水平。同样,表达阶段进行认知重评也降低了此阶段的恐惧水平,且显著抑制了恐惧记忆的自发恢复。结果提示,在面对应激时,个体如果能够成功地利用想象进行认知重评,就有可能避免应激事件对个体的心理或精神造成伤害。     

Effects of schedule of reinforcement on a pentobarbital discrimination in rats.

The purpose of this study was to determine the effects of the schedule of reinforcement on a pentobarbital discrimination in rats. Five rats were trained to discriminate 10 mg/kg pentobarbital from saline under a multiple fixed-interval 180-s fixed-ratio 20 schedule of reinforcement. During both saline and pentobarbital training sessions, subjects emitted a higher percentage of correct responses under the fixed-ratio component as compared to the fixed-interval component of the multiple schedule. Determination of the pentobarbital dose-response curve under the fixed-ratio component resulted in a steep curve characterized by responding on the saline lever at low doses and on the drug lever at higher doses. Under the fixed-interval component, a graded dose-effect curve was produced, with considerable responding on both levers after intermediate doses of pentobarbital. The administration of phencyclidine and MK-801 resulted in an intermediate level of drug-lever responding for some subjects. Administration of d-amphetamine resulted in saline (nondrug) appropriate responding. The results of this study demonstrate that the schedule of reinforcement is a determinant of drug stimulus control, just as it is a determinant of other drug effects.     

Human d-amphetamine drug discrimination: methamphetamine and hydromorphone.

Standard measures of subjective and discriminative effects of drugs were compared in 5 human volunteers. Subjects responded on a second-order color-tracking procedure, where 30 mg of d-amphetamine served as a discriminative stimulus for one response and its absence as the discriminative stimulus for another response. Self-reported subjective effects were assessed concurrently using the single-dose questionnaire, subscales of the Addiction Research Center Inventory, and several analogue rating scales. On different days following discrimination acquisition, varying doses of d-amphetamine, methamphetamine, and hydromorphone were administered. In these test sessions, either response was reinforced. Methamphetamine and d-amphetamine occasioned dose-related increases in d-amphetamine appropriate responding; hydromorphone did not. Methamphetamine and d-amphetamine occasioned dose-related increases in reports of the drug received being most like "speed"; hydromorphone occasioned dose-related increases in reports of the drug received being most like "dope." All three drugs occasioned dose-related increases in reports of drug liking, and increases in the morphine-benzedrine group, amphetamine, and benzedrine group scales of the Addiction Research Center Inventory. This experiment demonstrated that although explicit discriminative control of behavior by a drug may covary with drug identification, it does not necessarily covary with other self-reported subjective effects. Thus, the complementary nature of the data provided by drug discrimination and standard subjective-effects measures provides quantitative and qualitative data useful in studying both relatively novel compounds and the behavioral biology of psychoactive drugs in general.     

Synergistic effects of ethanol and cocaine on brain stimulation reward.

The effects of two widely abused drugs, ethanol and cocaine, were examined alone and in combination on intracranial reward processes. In agreement with previous research, higher doses of both cocaine and ethanol alone produced facilitation of behavior maintained by brain stimulation reward. Low intraperitoneal doses of ethanol and cocaine, which alone did not affect performance, were found to reduce stimulation reward threshold and modestly increase response rate. The enhancement of brain stimulation reward by the combination of ethanol and cocaine suggests that both drugs may produce their rewarding effects through common neuronal substrates and that they may potentiate the abuse of each other.     

Facilitation of human tobacco self-administration by ethanol: a behavioral analysis.

The effect of ethanol on the cigarette smoking of alcoholic subjects was studied in a residential laboratory. During daily 6-hr sessions, cigarettes were obtained either by request to the ward staff or by operation of a lever (fixed-ratio 5 or 10). In a mixed sequence across days, sessions involved ingestion of either vehicle (orange juice or vehicle plus ethanol (133.7 g). During ethanol sessions, the rate of cigarette smoking increased from 26% to 117% of vehicle levels. A series of control studies eliminated a number of potential behavorial mechanisms for the observed effect and indicated that the ethanol-induced increase in cigarette smoking occurred under a variety of experimental conditions: (1) when smoking could not occur concurrently with ethanol or vehicle consumption; (2) when subjects were not allowed to socialize; (3) when ingestion of ethanol or vehicle was scheduled for a number of consecutive days; (4) when various doses of ethanol were administered under blind conditions. In control experiments, weighing unsmoked tobacco and counting the number of puffs per cigarette indicated the effect was not due to smoking less of each cigarette. The effect was not limited to the experimental sessions alone, since total daily smoking was higher on ethanol days than vehicle days.     

Effects of discrete-trial and free-operant procedures on the acquisition and maintenance of successive discrimination in rats.

Rats were trained on a successive discrete-trial discrimination between two tonal stimuli to examine the effects of availability of a lever during intertrial intervals. In the discrete-trial condition, in which a lever was removed from the chamber during intertrial intervals, 10-s trials were initiated by the presentation of both discriminative stimulus and lever. In the free-operant condition, in which a lever was present during both trials and intertrial intervals, 10-s trials were initiated only by the presentation of a discriminative stimulus. Experiment 1 employed 50-s intertrial intervals and demonstrated that discriminative performances were acquired faster and maintained better in the free-operant conditions than in the discrete-trial conditions. Experiment 2 employed 5-s intertrial intervals and showed that poor discriminative performances in the discrete-trial conditions were improved. These results indicate that the presentation of a lever to start a trial can overshadow or mask the control by a discriminative stimulus and thereby obstruct the acquisition and maintenance of discriminative performances. Furthermore, the overshadowing or masking effects are strengthened as a function of the duration of intertrial intervals.     

Discrimination of methadone and cocaine by pigeons without explicit discrimination training.

Pigeons were trained to peck a key on a variable-interval 2-min schedule of food reinforcement. Prior to each session, either 2.0 mg/kg methadone (n = 3), 3.0 mg/kg cocaine (n = 4), or 5.6 mg/kg cocaine (n = 2) was administered. When each pigeon's rate of pecking was stable, a range of doses of the training drug and saline were administered prior to 20-min extinction sessions separated by at least four training sessions. Rate of pecking during these extinction tests was generally an increasing function of dose, with the lowest rates obtained following saline and low doses and the highest rates obtained following doses near the training doses. Dose functions from pigeons trained with 5.6 mg/kg cocaine were steeper than those from pigeons trained with 3.0 mg/kg cocaine. Pigeons trained with methadone or 3.0 mg/kg cocaine were then given discrimination training, in which food reinforcement followed drug administration and 20-min extinction sessions followed saline administration. Rates of pecking under these conditions quickly diverged until near-zero rates were obtained following saline and high rates were obtained following drug. Discrimination training steepened dose functions for the training drugs, and the effects of several other substituted drugs depended on the pharmacology of the training drug. The pigeons trained with 5.6 mg/kg cocaine were tested with d-amphetamine, methadone, and morphine prior to discrimination training. d-Amphetamine increased rates dose dependently, and methadone and morphine did not. The results suggest that discriminative control by methadone and cocaine was established without explicit discrimination training.     

Auditory discrimination: role of time and intensity in the precedence effect.

Rats were trained to respond on a lever adjacent to a sounding speaker (the sound source) when a single click was emitted. A second click (the artificial echo) was presented through a second speaker on the opposite side. In Condition I, the echo (equal in intensity to the source) was delayed from .015 to 32 milliseconds; greater than 75% correct responses were given for delay times between about .040 milliseconds (lower threshold) and 8 milliseconds (upper threshold). In Condition II, the echo (simultaneous with the source) was reduced in intensity relative to the source over a range from 2.5 decibels to 40 decibels; greater than 75% correct responses occurred for intensity reductions greater than 5 decibels. In Condition III, both the intensity and the delay time of the echo were manipulated in a manner analogous to that which would occur under natural conditions; greater than 95% correct responses were given for delay times from 1 to 32 milliseconds. These data indicate that both time and intensity differences are necessary for localization of primary sources, with delay time contributing more at short echo path distances, and intensity differences at long distances.     

The effects of schedule history and the opportunity for adjunctive responding on behavior during a fixed-interval schedule of reinforcement.

The effects of schedule history and the availability of an adjunctive response (polydipsia) on fixed-interval schedule performance were investigated. Two rats first pressed levers under a schedule of food reinforcement with an interresponse time greater than 11 s, and 2 others responded under a fixed-ratio 40 schedule. All 4 were then exposed to a fixed-interval 15-s schedule. Water was continuously available under these conditions, but after responding became stable on the fixed-interval schedule, access was experimentally manipulated. With water freely available, subjects did not display characteristic fixed-interval response rates and patterns (i.e., scalloping or break-and-run). Instead, they exhibited predictable, stable patterns of behavior as a function of their schedule histories: Subjects with the interresponse-time history exhibited low response rates, and those with the fixed-ratio history exhibited high rates. Manipulating the amount of water available resulted in marked changes in response rates for rats with the interresponse-time history but not for those with the fixed-ratio history. The results illustrate the multiple causation of behavior by its previous and current schedules of reinforcement and other concurrent factors.