Increasing Behavior With Conditioned Reinforcement

The mesolimbic dopamine system has been implicated in the primary reinforcing properties of drugs of abuse as well as in enhanced responding with conditioned reinforcement produced by psychomotor stimulant drugs. Despite clinical observations that nicotine self-administration (i.e. smoking) depends strongly upon conditioned reinforcement (i.e. cues support smoking behavior), little is known about whether nicotine directly affects motivational processes. In these experiments, we investigated whether acute nicotine would influence responding with conditioned reinforcement and the degree to which pretreatment with the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine would modify any nicotine-induced behavioral effects. After subjects had been trained to associate an initially neutral stimulus with water reward, they received acute nicotine (43,25-350 micro g/kg SC; -5 min) or saline injections and were tested on the acquisition of a new response for conditioned reinforcement paradigm. In separate experiments, the effect of pretreatment with the nicotinic acetylcholine receptor antagonist mecamylamine (300 or 1000 micro g/kg SC; -20 min) alone, or in combination with nicotine (350 micro g/kg SC; -5 min), on conditioned reinforcement was also examined. Acute nicotine injection produced a selective enhancement of responding with conditioned reinforcement (i.e. on the CR lever), without producing non-selective increases in overall responding. The effect of nicotine (350 micro g/kg SC; -5 min) was selectively blocked by mecamylamine (300 micro g/kg). These findings demonstrate that acute exposure to nicotine augments the control over behavior by a conditioned reinforcer, suggesting that nicotine may enhance motivational processes.

Nicotine can robustly increase responding for conditioned reinforcers (CRs), stimuli that acquire reinforcing properties based on association with primary reinforcers. Menthol and licorice are tobacco flavoring agents also found in sweet foods (eg, candy and ice cream), making them putative CRs before they are consumed in tobacco. We sought to determine if intravenous self-administration (IVSA) of nicotine was enhanced by the inclusion of oral tobacco flavor CRs. Menthol (160 or 320 µM) or licorice root extract (0.1% or 1%) were established as CRs (paired with 20% sucrose) or "neutral" stimuli (paired with water) in separate groups. During subsequent IVSA tests, nicotine was delivered in conjunction with oral presentations of the CR. In experiment 1, a menthol CR significantly shifted the peak nicotine dose from 15 µg/kg/infusion (Neutral group) to 3.25 µg/kg/infusion (CR group). In experiment 2, a menthol CR significantly increased operant licks for nicotine (3 µg/kg/infusion) relative to control groups. In experiment 3, both licorice and menthol CRs significantly increased operant licks for nicotine (7.5 µg/kg/infusion) relative to an "inactive" sipper. The licorice CR increased nicotine IVSA in proportion to the strength of the flavor, but both menthol concentrations increased nicotine IVSA to a similar extent. Tobacco flavor additives with conditioned reinforcing properties promote acquisition of nicotine self-administration at low unit doses and may have robust impact on tobacco consumption when nicotine yield is low. Tobacco flavor additives are found in rewarding foods (eg, ice cream) and gain palatability based on associations with primary rewards (eg, sugar) making them "conditioned reinforcers." Nicotine increases the motivation for flavor conditioned reinforcers and the present studies show that tobacco flavor additives can interact with nicotine to promote more nicotine self-administration. The interaction between flavors additives and nicotine may promote nicotine exposure and subsequently dependence.

Nicotine administration potentiates conditioned reinforcement in rats, an effect that persists for weeks after chronic exposure. Little is known regarding the nicotinic receptor subtypes that may mediate this effect. The purpose of this study was to determine whether beta2-subunit-containing nicotinic acetylcholine receptors (beta2*nAChRs) are necessary for lasting effects of nicotine on conditioned and primary reinforcement in mice. Beta2 knockout (beta2KO) and wild-type (WT) mice received 14 days of nicotine exposure (NIC, 200 microg/ml in 2% saccharin) or saccharin alone (SAC) in their drinking water. Five days later, mice received paired presentations of a conditioned stimulus (CS) with water unconditioned stimulus (US) or explicitly unpaired presentations of the CS and US during Pavlovian discriminative approach training. Training was followed by two conditioned reinforcement tests. Mice were subsequently tested for food-reinforced responding in the absence of explicit cues followed by a progressive ratio test. During conditioned reinforcement testing, only mice in the paired condition showed increased responding in the CS-reinforced aperture over inactive apertures. WT-NIC mice showed enhanced conditioned reinforcement compared to WT-SAC animals. beta2KO-SAC mice showed elevated conditioned reinforcement compared to WT-SAC subjects, but beta2KO-NIC and beta2KO-SAC mice did not differ in responding with conditioned reinforcement. Prior nicotine exposure did not alter food-reinforced responding but resulted in elevated break points for food in both genotypes. These data show that nicotine exposure enhances conditioned reinforcement in mice and indicate that beta2*nAChRs are necessary for nicotine-dependent enhancement of incentive aspects of motivation but not motivation for primary reinforcement measured by progressive ratio responding.

Combined with the project of an open cut metro tunnel passing through a viaduct, three- dimensional finite element method is applied to study the lateral deformation law of viaduct pile foundations induced by adjacent excavation in the pile foundations reinforcement and un-reinforcement conditions. The results show that the lateral deformation of pile foundations increases with the increasing of excavation depth. The closer distance and the larger deformation, the influence of pile foundations on excavation will be more obvious. The pile foundations deformation is significantly reduced when taking protection measures such as adding new piles, expanding the pile cap and strengthening stratum. Compared with the maximum deformation of the un-reinforcement condition, the reinforcement condition is only 27% to 30%, and the reinforcement measure is remarkably effective. In addition, the length of the piles, the depth of foundation pit, as well as the relative positions of walls and piles have significant influences on piles deformation forms, and it should be taken into account in the design and construction of foundation pit.

Repeated nicotine exposure during adolescence alters reward-related learning in male and female rats

Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of d-amphetamine

A conditioned reinforcer is a stimulus that acquires its reinforcing properties through association with a primary reinforcer (Hackenberg, 2018). Common examples include tokens in a token economy system (Tarbox et al., 2006), praise preceding the delivery of a toy to a child, and the sound of a click before an animal receives food (Skinner, 1969). Although extensive research has examined how variations in reinforcement parameters – such as magnitude, quality, and delay – affect response allocation, little research has explored the impact of other reinforcement characteristics, such as how a conditioned reinforcer is delivered (Hackenberg, 2009). Understanding how variations in conditioned reinforcer delivery methods influence the rate of responding and preference is essential for refining reinforcement-based interventions, particularly in applied settings (Sleiman et al., 2020). In the present study I examined whether the delivery method of a conditioned reinforcer affects response allocation. I exposed participants to two types of conditioned reinforcer delivery methods, delivering the conditioned reinforcer either in their hand or on the table. I then assessed whether a preference for one delivery method was created, and whether that preference could be reversed. Although some participants' behavior came under the control of a conditioned reinforcer delivery method, the majority did not. These findings suggest that further research is needed to determine how preference for conditioned reinforcer delivery methods is developed. Additionally, these results suggest the need for further analysis of the stimulus features organisms attend to and how these features influence response allocation.

Stimulant drugs have been shown to enhance the control over behaviour exerted by stimuli previously correlated with primary reinforcers, termed conditioned reinforcers (CR). Experiment 1 examined the possible neuroanatomical specificity of the enhancement of conditioned reinforcement following intracerebral injections of d-amphetamine. Thirsty rats were trained to associate a light with water. In the test phase, water was no longer presented but the light (CR) was intermittently produced by responding on one of two novel levers. Rats with bilateral guide cannulae aimed at the nucleus accumbens, posterior caudate nucleus, or medio-dorsal nucleus of the thalamus received four counterbalanced microinfusions of d-amphetamine (10, 20, 30 micrograms/2 microliters) or vehicle (control) over 4 test days. There was a dose-dependent selective increase in responding on the lever that produced the light (CR) with intra-accumbens d-amphetamine infusions. Quantitatively similar, but much more variable effects were found with intra-caudate infusions and no effects following intra-thalamic d-amphetamine. Experiment 2 provided evidence that the enhanced control over responding by a CR with intra-accumbens d-amphetamine is behaviourally specific. Three groups of rats received a compound tone--plus--light stimulus that was positively, negatively or randomly correlated with water during training. Intra-accumbens d-amphetamine produced selective increases in responding only if the contingent stimulus had been positively correlated. The results suggest that the nucleus accumbens may play an important role in d-amphetamine's enhanced control over behaviour exerted by conditioned reinforcers.

Dopamine release within the nucleus accumbens (NAcc) has been associated with both the rewarding and locomotor-stimulant effects of abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetamine-potentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After excitotoxic lesions that selectively destroyed either the NAcc core or shell, animals underwent additional CS-US training sessions and then were tested for the acquisition of a new instrumental response that produced the CS acting as a conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 microg) before each session. Shell lesions affected neither Pavlovian nor instrumental conditioning but completely abolished the potentiative effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals were impaired during the Pavlovian retraining sessions but showed no deficit in the acquisition of responding with CR. However, the selectivity in stimulant-induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine infusions dose-dependently increased responding on both the CR lever and a nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity and enhanced the locomotor-stimulating effect of amphetamine. These results indicate a functional dissociation of subregions of the NAcc; the shell is a critical site for stimulant effects underlying the enhancement of responding with CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is implicated in mechanisms underlying the expression of CS-US associations.

Individual differences exist in the attribution of incentive salience to conditioned stimuli associated with food. Here, we investigated whether individual differences also manifested with a Pavlovian alcohol conditioned stimulus (CS). We compiled data from five experiments that used a Pavlovian autoshaping paradigm and tests of conditioned reinforcement. In all experiments, male, Long-Evans rats with unrestricted access to food and water were acclimated to 15% ethanol. Next, rats received Pavlovian autoshaping training, in which a 10 s presentation of a retractable lever served as the CS and 0.2 mL of 15% ethanol served as the unconditioned stimulus (US). Finally, rats underwent conditioned reinforcement tests in which nose-pokes to an active aperture led to brief presentations of the lever-CS, but nose-pokes to an inactive aperture had no consequence. Rats were categorized as sign-trackers, goal-trackers and intermediates based on a response bias score that reflected their tendencies to sign-track or goal-track at different times during training. We found that distinct groups of rats either consistently interacted with the lever-CS (“sign-trackers”) or routinely approached the port during the lever-CS (“goal-trackers”) across a majority of the training sessions. However, some individuals (“shifted sign-trackers”) with an early tendency to goal-track later shifted to comparable asymptotic levels of sign-tracking as the group identified as sign-trackers. The lever-CS functioned as a conditioned reinforcer for sign-trackers and shifted sign-trackers, but not for goal-trackers. These results provide evidence of robust individual differences in the extent to which a Pavlovian alcohol cue gains incentive salience and functions as a conditioned reinforcer.

Endocannabinoids (eCBs) are critical gatekeepers of dopaminergic signaling, and disrupting cannabinoid receptor-1 (CB1) signaling alters DA dynamics to attenuate cue-motivated behaviors. Prior studies suggest that dopamine (DA) release plays a critical role in driving sign-tracking. Here, we determine whether systemic injections of rimonabant, a CB1 receptor inverse agonist, during Pavlovian lever autoshaping impair the expression of sign-tracking. We next examine whether rimonabant blocks the reinforcing properties of the Pavlovian lever cue in a conditioned reinforcement test. In Exp. 1, we trained rats in Pavlovian lever autoshaping prior to systemic rimonabant injections (0, 1, 3mg/kg) during early and late Pavlovian lever autoshaping sessions. In Exp. 2, we trained rats in Pavlovian lever autoshaping prior to systemic rimonabant injections (0, 1mg/kg) during a conditioned reinforcement test. Rimonabant dose-dependently decreased lever contact and probability, and increased sign-tracker's latency to approach the lever cue early in Pavlovian training. With extended training, many previously goal-tracking and intermediate rats shifted to lever approach, which remained dose-dependently sensitive to rimonabant. Rimonabant attenuated cue-evoked food cup approach early, but not late, in conditioning, and did not affect pellet retrieval or consumption. The inserted lever cue served as a robust conditioned reinforcer after Pavlovian lever autoshaping, and 1mg/kg rimonabant blocked conditioned reinforcement. Together, our results suggest that CB1 signaling mediates two critical properties of incentive stimuli; their ability to attract (Exp. 1) and their ability to reinforce (Exp. 2) behavior.

The effect of pimozide on conditioned reinforcement was determined by comparing rate of lever pressing for a tone in groups previously treated with or without the drug when the tone was paired with food. Eight groups of six to eight rats each received three phases of training in a two-lever box. The pre-exposure phase measured the operant rate of pressing the two levers, one of which produced a 3s tone. In the conditioning phase, with the levers absent, the tone was paired with food over four sessions. The test phase again measured the rate of pressing the two levers. In an undrugged experimental group (i.e., Paradigm group), the number of presses on the tone lever significantly increased from the pre-exposure to the test phase, thereby confirming that the procedure could establish conditioned reinforcement. A control group receiving tones and pellets randomly during the conditioning phase also showed conditioned reinforcement but a group receiving negatively correlated tones and pellets did not. Groups receiving the dopamine-receptor blocker pimozide (1.0 mg/kg) prior to each conditioning session failed to show conditioned reinforcement in the test session. Control groups ruled out state dependent learning and drug-induced performance impairments as explanations of this pimozide-related effect. These data may indicate a possible role for dopamine neurons in mediating the control of behavior by certain positive reinforcing stimuli.

Cholecystokinin-dopamine interactions within the nucleus accumbens in the control over behaviour by conditioned reinforcement

In the present study, excitatory backward conditioning was assessed in a conditioned reinforcement paradigm. The experiment was conducted with human subjects and consisted of five conditions. In all conditions, US reinforcing value (i.e. time reduction of a timer) was assessed in phase 1 using a concurrent FR schedule, with one response key leading to US presentation and the other key leading to no-US. In phase 2, two discrete stimuli, S+ and S−, were paired with US and no-US respectively using an operant contingency. For three groups, backward contingencies were arranged, and two of these were designed to rule out a trace (forward) conditioning interpretation of the results. The two other groups served as control conditions (forward and neutral conditions). Finally, in phase 3 for all groups the CSs were delivered in a concurrent FR schedule similar to phase 1, but with no US. Responding during phase 3 showed conditioned reinforcement effects and hence excitatory backward conditioning. Implications of the results for conditioned reinforcement models are discussed.

Effects of novelty and methamphetamine on conditioned and sensory reinforcement