Nicotine trained as a negative feature passes the retardation-of-acquisition and summation tests of a conditioned inhibitor (original) (raw)
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The Conditional Stimulus Effects of Nicotine Vary As a Function of Training Dose
Behavioural pharmacology, 2007
Previous studies have shown that the interoceptive nicotine conditional stimulus (CS) functions similarly to exteroceptive CSs such as lights or environments. For instance, the appetitive conditioned response (CR) evoked when nicotine is repeatedly paired with sucrose presentations (the unconditioned stimulus; US) is sensitive to changes in training dose (CS salience) and the contiguity between the CS effects and sucrose. The current study was conducted to extend this research by examining the possible role of US intensity in CR acquisition and maintenance. Rats were trained using one of four sucrose concentrations: 0, 4, 16, or 32% (w/v). On nicotine sessions (0.4 mg base/kg), rats received 36 deliveries (4 s each) of their assigned concentration intermittently throughout the session; sucrose was withheld on saline sessions. In all groups, an appetitive goal-tracking CR was acquired at a similar rate. However, the asymptotic CR level varied with sucrose concentration. The magnitude of the CR was increased in rats trained with higher sucrose US concentrations. These findings are consistent with previous Pavlovian conditioning research, and extend the conditions under which the nicotine state functions as an interoceptive conditional stimulus.
Interoceptive conditioning with the nicotine stimulus
Behavioural Pharmacology, 2013
Interoceptive conditioning involving the nicotine stimulus likely contributes to chronic tobacco use. To better understand the nature of this interoceptive conditioning, we compared generalization during repeated extinction with generalization in a 'transfer of extinction' test using a wide range of test doses. Rats were first trained in the discriminated goal-tracking task in which nicotine (0.2 or 0.4 mg/kg), but not saline, was paired with repeated intermittent access to sucrose. Across sessions, nicotine acquired control of approach behavior directed at the location of previous sucrose deliveries. Extinction followed with eight 20-min sessions without sucrose access; extinction doses of nicotine ranged from 0.05 to 0.6 mg/kg. In rats trained with 0.4 mg/kg, the 0.1, 0.2, and 0.6 mg/kg doses evoked comparable responding across extinction sessions; substitution was only partial at 0.05 and 0.075 mg/kg (i.e. above saline controls, but less than the training dose). With the 0.2 mg/kg training dose, complete generalization was seen only at the 0.1 and 0.4 mg/kg doses. After extinction, rats were given a transfer test with their training dose. Rats trained with 0.4 mg/kg showed full transfer of extinction learning with 0.1, 0.2, and 0.6 mg/kg (i.e. responding comparable with extinction with the training dose). Partial transfer was observed at 0.075 mg/kg. With the 0.2 mg/kg nicotine dose, only 0.4 mg/kg fully generalized; 0.075, 0.1, and 0.6 mg/kg showed partial transfer. Extinction with 0.05 mg/kg dose did not show transfer to either training dose. These findings indicated that conclusions regarding stimulus similarity across nicotine doses can vary with testing protocol.
Psychopharmacology, 2006
Rationale Pavlovian feature negative discriminations have been widely used to understand inhibitory conditioning processes using exteroceptive stimuli. Comparatively little is known about inhibitory conditioning processes using a drug state as a negative feature. A negative feature signals that presentation of a conditional stimulus (CS) will not be paired with an unconditioned stimulus. Objectives: The present research examined whether nicotine served as a negative feature and started characterizing its properties. Methods and results: In acquisition, rats received intermixed saline and nicotine (0.4 mg/kg, base) sessions. On saline sessions, a 15-s light CS was paired with 4-s access to sucrose; the CS was presented on nicotine sessions, but sucrose was withheld. The discrimination was acquired with more goal tracking during the CS on saline sessions. Nicotine's inhibition of this conditioned response (CR) was sensitive to nicotine dose (ED 50 =0.225) and injection to testing interval (CR returned at 200 min). Mecamylamine pretreatment, but not hexamethonium, produced a loss of inhibitory control by nicotine suggesting a role for central nicotinic acetylcholine receptors. Amphetamine, bupropion, arecoline, and chlordiazepoxide, but not caffeine, substituted for the nicotine feature. However, in locomotor tests, amphetamine and bupropion increased activity; arecoline and chlordiazepoxide decreased activity. For this reason, the motor effects of these ligands could not be dissociated from substitution via shared stimulus properties. Conclusions: This feature negative task provides a preclinical model for studying how drug states inhibit responding, although identifying the process(es) mediating CR inhibition will require further research.
Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus
European journal of pharmacology, 2007
Although past research has shown that the interoceptive effects of nicotine serve as a conditional stimulus using sucrose as the unconditioned stimulus, very little is known about the importance of dose. Accordingly, rats were assigned to 0.1, 0.2, or 0.4 mg nicotine base/kg as the training dose. Sucrose (4-s access) was delivered 36 times on nicotine sessions; sucrose was withheld on intermixed saline sessions. The discrimination was acquired for all groups, as measured by more photobeam breaks in the dipper receptacle before the first sucrose delivery on nicotine sessions, compared with a similar interval on saline sessions. Thirty nicotine sessions without sucrose deliveries (extinction) decreased conditioned responding with the 0.4 mg/kg dose maintaining higher responding than the lower doses. After reestablishing discrimination performance, rats were tested with their training dose at various injection-to-placement intervals. Conditioned responding diminished with longer intervals; 0.4 mg/kg nicotine-evoked conditioned responding at longer intervals. Subsequent generalization testing with nicotine or saline at the 5-min training interval found that conditioned responding was evoked by lower test doses in the 0.1 mg/kg group than in the other groups. Combined, this research demonstrates that the nicotine conditional stimulus shows some variation with training dose.
Behavioural processes, 2009
Previous studies have shown that the interoceptive nicotine conditional stimulus (CS) functions similarly to exteroceptive CSs such as lights or environments. For instance, the appetitive conditioned response (CR) evoked when nicotine is repeatedly paired with sucrose presentations (the unconditioned stimulus; US) is sensitive to changes in training dose (CS salience) and the contiguity between the CS effects and sucrose. The current study was conducted to extend this research by examining the possible role of US intensity in CR acquisition and maintenance. Rats were trained using one of four sucrose concentrations: 0, 4, 16, or 32% (w/v). On nicotine sessions (0.4 mg base/kg), rats received 36 deliveries (4 s each) of their assigned concentration intermittently throughout the session; sucrose was withheld on saline sessions. In all groups, an appetitive goal-tracking CR was acquired at a similar rate. However, the asymptotic CR level varied with sucrose concentration. The magnitude of the CR was increased in rats trained with higher sucrose US concentrations. These findings are consistent with previous Pavlovian conditioning research, and extend the conditions under which the nicotine state functions as an interoceptive conditional stimulus.
Nicotine administration enhances conditioned inhibition in rats
European Journal of Pharmacology, 2006
The effect of nicotine on conditioned inhibition was examined using a serial feature negative discrimination task. Nicotine (0.35mg/kg) or vehicle was administered before each of 16 training sessions. On some trials in each session, a tone was presented and followed by food reward. On other trials, the tone was preceded by a visual stimulus and not reinforced. Nicotine-treated rats exhibited greater discrimination between the two trial types as evidenced by less frequent responding during non-reinforced trials, and learned the discrimination in fewer sessions than vehicle-treated rats. In contrast, there were no group differences in responding during the reinforced trials.
Behavioural brain research, 2011
Previous research has shown that a nicotine conditional stimulus (CS) can compete with (i.e., overshadow) a brief light CS. Another form of competition, blocking, has not yet been examined with the nicotine CS. Groups of rats were assigned to an element training condition. For the N+ group, during each daily 2 h element training session, there were ten intravenous nicotine infusions (0.03 mg/kg) followed 30 s later with 4 s access to sucrose. In the N− group, nicotine and sucrose presentations were explicitly unpaired. The chamber alone group (C alone) had no stimulus presentations. Element training was followed by compound training in all groups. A 30-s houselight was included during the time between the nicotine infusion and paired sucrose delivery. Non-reinforced element presentations assessed relative control of the goal tracking conditioned response (CR). The N+ group showed a higher proportion of CR control by the nicotine than the light. The opposite pattern was found in the N− and C alone groups indicating that nicotine CS controlled less of the CR than the light. Thus, excitatory conditioning with the nicotine CS blocked later conditioning to the light. This finding adds to literature examining the interaction between interoceptive drug CSs and other environmental stimuli.
Neuropharmacology, 2010
The interoceptive stimulus effects of nicotine acquire control over behavior. This observation, among others, suggests that the stimulus effects of nicotine are important in the development and tenacity of tobacco dependence. Despite this importance, there has been little research examining whether nonreinforced presentations (extinction) of a ligand that share stimulus effects of nicotine will weaken responding controlled by nicotine. Rats were trained to discriminate nicotine (0.4 mg/kg) from saline using a discriminated goal-tracking task in which nicotine signaled intermittent access to sucrose; sucrose was withheld on saline sessions. Experiment 1 examined substitution for nicotine by ABT-418, nornicotine, epibatidine, varenicline, or cytisine in 4-min extinction tests. Experiments 2e5 [low-dose nicotine (0.05 mg/kg), ABT-418, nornicotine, or varenicline, respectively] examined whether substitution for nicotine would persist if extinction tests were increased to 20 min and repeated daily for 6 days. Finally, generalization of this extinction back to the nicotine training stimulus was assessed. Full substitution in brief 4-min extinction tests was seen for ABT-418, nornicotine, epibatidine, varenicline, and cytisine. Low-dose nicotine, ABT-418, nornicotine, and varenicline, evoked only a partial 'nicotinelike' response in the first 20-min extinction test. With repeated extinction, only low-dose nicotine, nornicotine, and varenicline continued to substitute. Extinction with nornicotine and varenicline transferred back to nicotine as indicated by a partial conditioned response to the training stimulus. Interpretations regarding 'nicotine-like' effects of a ligand depend on the nature of the test. Understanding the processes mediating transfer of extinction learning with potential pharmacotherapies may reveal new treatment targets.
Psychopharmacology, 2010
Rationale Research using a drug discriminated goaltracking (DGT) task showed that the N-methyl-D-aspartate (NMDA) channel blocker MK-801 (dizocilpine) reduced the nicotine-evoked conditioned response (CR). Objectives Given the unknown mechanism of the effect, Experiment 1 replicated the MK-801 results and included tests with NMDA receptor ligands. Experiments 2a and 2b tested whether MK-801 pretreatment blocked DGT via a state-dependency effect. Methods In Experiment 1, adult male Sprague-Dawley rats received intermittent access to liquid sucrose following nicotine (0.4 mg base/kg); no sucrose was delivered on intermixed saline sessions. Conditioning was indicated by increased anticipatory dipper entries (goal-tracking) on nicotine compared to saline sessions. Antagonism and/or substitution tests were conducted with MK-801, phencyclidine, CGP 39551, d-CPPene (SDZ EAA 494), Ro 25,6981, L-701,324, ACPC, and NMDA. In Experiment 2a, rats received nicotine and sucrose on every session-no intermixed saline sessions without sucrose. Tests combined MK-801 or the non-competitive nicotinic acetylcholine receptor antagonist, mecamylamine with either nicotine or saline. Experiment 2b had sucrose delivered on saline sessions and no sucrose on intermixed nicotine sessions followed by MK-801 antagonism tests of the saline CS.