Rationale
Smoking typically begins during adolescence and is largely reinforced by social cues. During adolescence in rats, sensitivity to both social cues and drugs of abuse is enhanced.
Objectives
...We have previously demonstrated in adolescent male rats that a low dose of cocaine interacts with social reward to produce an enhanced conditioned place preference (CPP) relative to either reward given alone. The present study further examined the nature of drug–social reward interactions using nicotine.
Methods
Dose–effect functions for nicotine-CPP were established using two different routes of administration (vehicle, 0.1, 0.3, and 0.6 mg/kg, SC and vehicle, 0.01, 0.03, and 0.06 mg/kg, IV). The effects of nicotine on social reward-CPP and social play behavior were next examined using parameters presumed to be sub-threshold for establishing social reward- and nicotine-CPP.
Results
Dose-dependent nicotine-CPP was observed using both routes of administration. Two pairings of the initially non-preferred side of the apparatus with either SC nicotine or another adolescent rat failed to produce CPP when examined alone, but together produced a robust CPP despite nicotine reducing social play. This interaction effect was not observed with the IV nicotine. A final experiment demonstrated that the enhancement of CPP with the combination of rewards was not due to additive effects of weak, sub-threshold conditioning.
Conclusions
These findings suggest that nicotine and social rewards interact synergistically in adolescent rats resulting in a greater, perhaps qualitatively different, reward than either reward given alone. Understanding drug–social reward interactions may provide new directions for development of preventions and interventions of adolescent smoking.
•Lever pressing was reinforced on a variable-interval 30-s schedule in rats.•The bi-exponential refractory model described instrumental responding at six lever heights.•Lower and intermediate lever ...heights produced longer bouts and faster between- and within-bout responding.•These data suggest the influence of the body size on the organization of the operant.
The effect of lever height on the temporal organization of reinforced lever pressing was examined. Lever pressing was reinforced on a variable-interval 30-s schedule in rats, with lever height manipulated across six successive conditions. Parameters of the organization of responses in bouts (bout length distribution, bout-initiation rate, within-bout rate, and sequential dependency) were estimated. These estimates revealed (1) a qualitative change in the distribution of IRTs and their sequential dependency when the lever was too high, (2) a mixture of geometrically-distributed bout lengths at all lever heights, and (3) longer bouts at lower and intermediate lever heights. In accordance with previous data, these findings suggest that lower and intermediate lever heights favored lever pressing with longer bout lengths, faster bout initiation, faster within-bout responding, and more sequentially dependent timing. These results underscore the disociability of motoric capacity in operant performance, and may reflect the influence of the body size on the temporal organization of the operant.
Response bouts are clusters of responses that occur in rapid succession and are punctuated by pauses during which the response does not occur. Under variable interval schedules of reinforcement, the ...number of responses in each bout (the bout length) varies among bouts. This experiment was aimed at determining whether the relative rate of reinforcement influenced the relative frequency of bouts of different lengths. Lever pressing in rats was reinforced under a tandem variable time (VT) 150-s fixed ratio (FR) X, where X could be 1 or 5 and varied randomly after each reinforcer. Two conditions were included: majority FR1 (mFR1) and majority FR5 (mFR5). In mFR1, 75% of reinforcers had a tandem FR requirement of 1 and 25% had a tandem FR requirement of 5; this distribution was reversed in mFR5. The dynamic bi-exponential refractory model of response bouts was fitted to the interresponse times (IRTs) in each condition. Model parameter estimates and IRTs were then used to simulate probable distributions of bout lengths. These distributions comprised a mixture of short geometrically-distributed bout lengths and long negative-binomially-distributed bout lengths. Long bouts were significantly longer in the mFR5 condition than in the mFR1 condition. In conjunction with previous data, the present study suggests that the prevalence of long bouts increases with the proportion of reinforcers with FR5 requirement. These results suggest that bouts of different lengths are sensitive to the rate at which they are reinforced.
Abstract Adolescence is a period of enhanced sensitivity to social influences and vulnerability to drug abuse. Social reward in adolescent rats has been demonstrated with the conditioned place ...preference (CPP) model, but it is not clear whether limited contact with another rat without play is sufficient to produce reward. We investigated this issue using an apparatus containing two main compartment, each with a wire mesh barrier that allowed rats placed on either side of the barrier to have limited physical contact. Adolescent male rats were given two conditioning sessions/day for 2 or 8 days following baseline preference tests. Rats were placed into their preferred side alone for one daily 10-min session and into their initially non-preferred side (i.e., CS) for the other session during which they either had restricted or unrestricted physical access to another rat (Rat/Mesh or Rat/Phys, respectively) or to a tennis ball (Ball/Mesh or Ball/Phys, respectively) unconditioned stimulus (US). Only the Rat/Phys group exhibited CPP after 2 CS–US pairings; however, after 8 CS–US pairings, the Rat/Mesh and Ball/Phys groups also exhibited CPP. During conditioning, the rat US elicited more robust approach and contact behavior compared to the ball, regardless of physical or restricted access. The incidence of contact and/or approach increased as the number of exposures increased. The results suggest that the rank order of US reward efficacy was physical contact with a rat > limited contact with a rat > physical contact with a ball, and that rough-and-tumble play is not necessary to establish social reward-CPP. The findings have important implications for emerging drug self-administration models in which two rats self-administering drug intravenously have limited physical contact via a mesh barrier shared between their respective operant conditioning chambers.
Operant hyperactivity, the emission of reinforced responses at an inordinately high rate, has been reported in children with ADHD and in the Spontaneously Hypertensive Rat (SHR), the most widely ...studied animal model of ADHD. The SHR emits behavior at hyperactive levels, relative to a normoactive strain, only when such behavior is seldom reinforced. Because of its dependence on rate of reinforcement, operant hyperactivity appears to be driven primarily by incentive motivation, not motoric capacity. This claim was evaluated in the present study using a novel strategy, based on the organization of behavior in bouts of reinforced responses separated by pauses.
Male SHR, Wistar-Kyoto (WKY) and Wistar rats (WIS) were exposed each to a multiple variable-interval schedule of sucrose reinforcement (12, 24, 48, 96, and 192 s) between post-natal days (PND) 48 and 93. Responding in each schedule was examined in two epochs, PND 58-62 and 89-93. Parameters of response-reinforcement functions (Herrnstein's hyperbola) and bout-organized behavior were estimated in each epoch.
SHR emitted higher response rates than WKY and WIS, but only when rate of reinforcement was low (fewer than 2 reinforcers per minute), and particularly in the second epoch. Estimates of Herrnstein's hyperbola parameters suggested the primacy of motivational over motoric factors driving the response-rate differential. Across epochs and schedules, a more detailed analysis of response bouts by SHR revealed that these were shorter than those by WKY, but more frequent than those by WKY and WIS. Differences in bout length subsided between epochs, but differences in bout-initiation rate were exacerbated. These results were interpreted in light of robust evidence linking changes in bout-organization parameters and experimental manipulations of motivation and response-reinforcement contingency.
Operant hyperactivity in SHR was confirmed. Although incentive motivation appears to play an important role in operant hyperactivity and motoric capacity cannot be ruled out as a factor, response-bout patterns suggest that operant hyperactivity is primarily driven by steeper delay-of-reinforcement gradients. Convergence of this conclusion with theoretical accounts of ADHD and with free-operant performance in children with ADHD supports the use of SHR as an animal model of ADHD.
•The organization of operant behavior was disrupted in two strains of rat.•Extinction progressively reduced the rate at which response bouts were initiated.•Non-contingent reinforcement progressively ...reduced the length of response bouts.•Pre-feeding abruptly reduced the rate at which response bouts were initiated.•Analyses focused on response rate obscure key features of behavioral persistence.
Operant behavior appears to be organized in bouts of responses, whose parameters are differentially sensitive to various manipulations. This study investigated potential differential effects of three forms of operant response disruption—extinction (EXT), non-contingent reinforcement (NCR), and prefeeding (PRE)—on response bouts. In Experiment 1, Wistar Kyoto rats (WKY) were trained on a tandem variable-time (VT) 120s fixed-ratio (FR) 5 schedule of reinforcement; after stability was established, their responding was disrupted for three sessions with one of the three disrupters (EXT, NCR, or PRE). In Experiment 2, Long Evans (LE) rats were trained on a tandem VT 240s FR 5 to stability, and their responding disrupted with EXT or NCR. In EXT and NCR, response rates declined significantly and progressively over the course of the session, primarily due to a declining bout-initiation rate in EXT, and to fewer responses per bout in NCR. In contrast, a session-wide drop in response rate was observed in PRE, primarily due to a reduction in bout-initiation rate at the start of the session. These findings suggest that each form of disruption differentially impacts dissociable aspects of behavior. Theories of behavioral persistence should account for these functional relations, which appear to be obscured in response rate measures.
The inability to inhibit reinforced responses is a defining feature of ADHD associated with impulsivity. The Spontaneously Hypertensive Rat (SHR) has been extolled as an animal model of ADHD, but ...there is no clear experimental evidence of inhibition deficits in SHR. Attempts to demonstrate these deficits may have suffered from methodological and analytical limitations.
We provide a rationale for using two complementary response-withholding tasks to doubly dissociate impulsivity from motivational and motor processes. In the lever-holding task (LHT), continual lever depression was required for a minimum interval. Under a differential reinforcement of low rates schedule (DRL), a minimum interval was required between lever presses. Both tasks were studied using SHR and two normotensive control strains, Wistar-Kyoto (WKY) and Long Evans (LE), over an overlapping range of intervals (1 - 5 s for LHT and 5 - 60 s for DRL). Lever-holding and DRL performance was characterized as the output of a mixture of two processes, timing and iterative random responding; we call this account of response inhibition the Temporal Regulation (TR) model. In the context of TR, impulsivity was defined as a bias toward premature termination of the timed intervals.
The TR model provided an accurate description of LHT and DRL performance. On the basis of TR parameter estimates, SHRs were more impulsive than LE rats across tasks and target times. WKY rats produced substantially shorter timed responses in the lever-holding task than in DRL, suggesting a motivational or motor deficit. The precision of timing by SHR, as measured by the variance of their timed intervals, was excellent, flouting expectations from ADHD research.
This research validates the TR model of response inhibition and supports SHR as an animal model of ADHD-related impulsivity. It indicates, however, that SHR's impulse-control deficit is not caused by imprecise timing. The use of ad hoc impulsivity metrics and of WKY as control strain for SHR impulsivity are called into question.
Eckard and Lattal’s Perspectives on Behavior Science, 43(1), 5–19 (
2020
) critique of internal clock (IC) mechanisms is based on narrow concepts of clocks, of their internality, of their mechanistic ...nature, and of scientific explanations in general. This reply broadens these concepts to characterize all timekeeping objects—physical and otherwise—as clocks, all intrinsic properties of such objects as internal to them, and all simulatable explanations of such properties as mechanisms. Eckard and Lattal’s critique reflects a restrictive billiard-ball view of causation, in which environmental manipulations and behavioral effects are connected by a single chain of contiguous events. In contrast, this reply offers a more inclusive stochastic view of causation, in which environmental manipulations are probabilistically connected to behavioral effects. From either view of causation, computational ICs are hypothetical and unobservable, but their heuristic value and parsimony can only be appreciated from a stochastic view of causation. Billiard-ball and stochastic views have contrasting implications for potential explanations of interval timing. As illustrated by accounts of the variability in start times in fixed-interval schedules of reinforcement, of the two views of causality examined, only the stochastic account supports falsifiable predictions beyond simple replications. It is thus not surprising that the experimental analysis of behavior has progressively adopted a stochastic view of causation, and that it has reaped its benefits. This reply invites experimental behavior analysts to continue on that trajectory.
Dissociating motoric and motivational effects of pharmacological manipulations on operant behavior is a substantial challenge. To address this problem, we applied a response‐bout analysis to data ...from rats trained to lever press for sucrose on variable‐interval (VI) schedules of reinforcement. Motoric, motivational, and schedule factors (effort requirement, deprivation level, and schedule requirements, respectively) were manipulated. Bout analysis found that interresponse times (IRTs) were described by a mixture of two exponential distributions, one characterizing IRTs within response bouts, another characterizing intervals between bouts. Increasing effort requirement lengthened the shortest IRT (the refractory period between responses). Adding a ratio requirement increased the length and density of response bouts. Both manipulations also decreased the bout‐initiation rate. In contrast, food deprivation only increased the bout‐initiation rate. Changes in the distribution of IRTs over time showed that responses during extinction were also emitted in bouts, and that the decrease in response rate was primarily due to progressively longer intervals between bouts. Taken together, these results suggest that changes in the refractory period indicate motoric effects, whereas selective alterations in bout initiation rate indicate incentive‐motivational effects. These findings support the use of response‐bout analyses to identify the influence of pharmacological manipulations on processes underlying operant performance.
•Rats learn and use multiple timing cues simultaneously.•Behavioral control selectively shifts between timing and non-timing cues.•Performance might alternate between timing and non-timing ...strategies.•Non-timing in the midsession reversal involves a win-stay/lose-some-shift strategy.
In a midsession reversal task, subjects choose between two stimuli on every trial; only responses to one stimulus are reinforced. Halfway throughout the session, contingencies are reversed: previously reinforced responses are now extinguished and vice versa. Both, the outcome of the previous trial and the time elapsed since the beginning of the session, may predict the availability of reinforcement and determine choice. Thus, this task has typically been used to study cognitive flexibility and the temporal organization of behavior. This study assessed how past outcomes and time interact for behavioral control when each cue predicts the availability of reinforcement to a different extent. Eight rats were trained in four variations of the midsession reversal task differing in the reliability of outcomes and time as predictors of the reinforced response. We manipulated the reliability of the outcomes by providing either continuous or partial reinforcement, and the reliability of time by fixing the moment of reversal (middle of the session) or making the reversal unpredictable (semi-random trial). Results suggest that behavioral control alternates between outcomes and time according to the relative reliability of each cue. Model simulations show that outcomes and time may jointly determine behavior, and that momentary reinforcement rate may determine their relative influence.
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