Runway Trials Research Articles

Noradrenergic β-Receptor Antagonism within the Central Nucleus of the Amygdala or Bed Nucleus of the Stria Terminalis Attenuates the Negative/Anxiogenic Effects of Cocaine

Cocaine has been shown to produce both initial rewarding and delayed anxiogenic effects. Although the neurobiology of cocaine's rewarding effects has been well studied, the mechanisms underlying its anxiogenic effects remain unclear. We used two behavioral assays to study these opposing actions of cocaine: a runway self-administration test and a modified place conditioning test. In the runway, the positive and negative effects of cocaine are reflected in the frequency of approach-avoidance conflict that animals develop about entering a goal box associated with cocaine delivery. In the place conditioning test, animals develop preferences for environments paired with the immediate/rewarding effects of cocaine, but avoid environments paired with the drug's delayed/anxiogenic actions. In the present study, these two behavioral assays were used to examine the role of norepinephrine (NE) transmission within the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST), each of which has been implicated in drug-withdrawal-induced anxiety and stress-induced response reinstatement. Rats experienced 15 single daily cocaine-reinforced (1.0 mg/kg, i.v.) runway trials 10 min after intracranial injection of the β1 and β2 NE receptor antagonists betaxolol and ICI 118551 or vehicle into the CeA or BNST. NE antagonism of either region dose dependently reduced approach-avoidance conflict behavior compared with that observed in vehicle-treated controls. In addition, NE antagonism selectively interfered with the expression of conditioned place aversions while leaving intact cocaine-induced place preferences. These data suggest a role for NE signaling within the BNST and the CeA in the anxiogenic actions of cocaine.

Ethanol consumption reduces the adverse consequences of self-administered intravenous cocaine in rats

Human drug users report that the initial positive effects of cocaine are followed by a dysphoric state characterized by anxiety and drug-craving. As a means of presumably attenuating these negative aftereffects, 50-90% of cocaine users choose to co-administer ethanol during cocaine binges. This co-administration reportedly prolongs the "high" and diminishes the "low" associated with cocaine use. The current study was intended to assess whether this phenomenon could be modeled in the animal laboratory. We have previously shown that animals running a straight alley for an intravenous cocaine reward develop a unique approach-avoidance "conflict" behavior that is characterized by stop and retreat behaviors as the subjects approach the goal box. The retreats are thought to reflect the concurrent positive (reward) and negative (anxiety) associations with the goal box and can be dose-dependently reduced by pretreatment with diazepam, which presumably attenuates the anxiety stemming from the conflict. To test the role of ethanol in reducing cocaine-induced anxiety, rats were trained to run a straight-arm alley for a single daily injection of cocaine (1.0 mg/kg IV). Rats that had the opportunity to then drink either an 8% or a 4% sucrose-ethanol solution immediately following their daily runway trial came to exhibit fewer retreats than rats that did not drink ethanol following their cocaine injection. These results suggest that ethanol effectively reduces the development of approach-avoidance conflict in animals running an alley for IV cocaine, a result that may account for the prevalence of cocaine-ethanol co-administration in humans.

Sexually conditioned incentives:: Attenuation of motivational impact during dopamine receptor antagonism

The motivational impact of sexually conditioned incentives was examined in two experiments. In Experiment 1, male Long–Evans rats copulated to ejaculation in the presence of one of two scents (orange or almond extract) on five separate occasions. On alternating days, subjects spent an equal amount of time in social isolation with the opposing scent. Following the 10-day conditioning regimen, subjects ran more rapidly down an operant runway toward a goalbox containing the sex-paired scent (CS+) compared to trials on which the isolation-paired scent (CS−) or no scent was provided. In Experiment 2, comparably conditioned male rats were first given a baseline runway trial with an unscented goalbox. The following day, subjects were pretreated with one of four doses of haloperidol (0.0, 0.075, 0.15, or 0.30 mg/kg ip) 45 min prior to being tested in the runway for their motivation to approach either the CS+ or CS− scents. Control subjects given vehicle injections performed comparably to subjects from Experiment 1, taking significantly less time to approach the CS+ than an unscented goalbox. This decrease in run latency was not observed in subjects within the 0.075 and 0.15 mg/kg haloperidol groups. Subjects in the 0.30 mg/kg haloperidol groups took significantly more time to approach both the CS+ and CS− compared to their baseline run times. These data reveal that an olfactory cue associated with sexual reward becomes a conditioned incentive capable of eliciting approach behavior, and that dopamine receptor antagonism (at moderate but not high doses) selectively attenuates this cue-induced motivation.

Impairment of working memory by neuronal degeneration with NMDA in rat hippocampal CA-1

Rats were trained on a three-panel runway task prior to injections of N-methyl-D-aspartate (NMDA; 40nmoles/µl/side) into the dorsal hippocampus. One week after the treatment, animals did not show any change in the number of errors on the first runway trial (reference memory), with one correct white and two incorrect black panels at each choice point, whereas they showed a marked increase in the number of errors on the following (2nd-6th) trials (working memory) with all black panels. The memory deficit persisted at least for 10 days. After the experiments, histological studies showed neuronal degeneration of hippocampal CA-1 pyramidal cells in all NMDA-treated rats but not in vehicle-treated rats. Pretreatment with the NMDA receptor antagonist MK-801 (3 or 10mg/kg, i.p) before the NMDA injections protected both the neuronal degeneration and the memory deficit. These findings suggest that selective neuronal degeneration induced by excessive stimulation of NMDA receptors in hippocampal CA-1 impaired working memory, but not reference memory.

Goal aversiveness after escape training with short and long intertrial intervals

Different intertriai intervals (ITIs) may influence the aversiveness of the goal area in aversive training with one-way procedures. That possibility was explored. Albino rats were given 20 shock-escape runway trials with short or long ITIs followed by 5 extinction test trials with goalbox measures for latency to eat, climb out, and move onto a wood floor. Different measures produced different outcomes. “Time to eat” did not differentiate groups. Massed-trials animals were quicker to “move over” initially but slowed down over trials. Spaced and massed procedures did not produce initial differences on “climb out,” but spaced-trials animals speeded up over trials and massed-trials animals slowed down. Results suggested that differences in ITIs did not generate major differences in levels of aversion in the “safe” area. ITI effects on performance may be due to differential effects on the conditioning process.

Numerical and Sensory Categorization of Serial Information by Animals

Rats were trained in a straight runway on a series consisting of 4 elements, each element being defined in terms of the number of .045-gm. Noyes pellets used as reward on 4 runway trials separated by about 20 sec. The series elements were 2, 6, 12, and 0 (2-6-12-0). The animals were trained each day on 3 such series, the series themselves being separated within a day by about 12 min. for 28 days before introducing a new transfer series to assess the relevance of the order of the series elements. In previous experiments with the simpler series, 2-12-0, alterations in order of elements eliminated the animals' tendencies to run much slower to the terminal nonreward element of the series, but transfer was clearly shown here when we shifted from 2-6-12-0 to 6-12-2-0. That is, the animals continued on the transfer test to approach the terminal element slowly, a result which we interpret as supporting the view that the rats either counted the rewarded trials and used that count to predict terminal nonreward, or they behaved on the basis of cues associated with the ordinal position of the trial.

NUMERICAL AND SENSORY CATEGORIZATION OF SERIAL INFORMATION BY ANIMALS

Rats were trained in a straight runway on a series consisting of 4 elements, each element being defined in terms of the number of .045-gm. Noyes pellets used as reward on 4 runway trials separated by about 20 sec. The series elements were 2, 6, 12, and 0 (2-6-12-0). The animals were trained each day on 3 such series, the series themselves being separated within a day by about 12 min. for 28 days before introducing a new transfer series to assess the relevance of the order of the series elements. In previous experiments with the simpler series, 2-12-0, alterations in order of elements eliminated the animals' tendencies to run much slower to the terminal nonreward element of the series, but transfer was clearly shown here when we shifted from 2-6-12-0 to 6-12-2-0. That is, the animals continued on the transfer test to approach the terminal element slowly, a result which we interpret as supporting the view that the rats either counted the rewarded trials and used that count to predict terminal nonreward, or they behaved on the basis of cues associated with the ordinal position of the trial.

Organized responding in instrumental learning: Chunks and superchunks

Two investigations attempted to determine if rats could learn that the second series of runway trials, the test series, was the same as the first series, the study series. Series were constructed from runway responses which terminated either in food reward (R) or nonreward (N). In the series RNR, for example, three successive responses terminated in R, N, and R, respectively. Rats manifested mastery of a series by running fast to R and slow to N. In Experiment 1 the test series (either RNR or RNN) occurred in a black runway about 15 s after the study series presented in a white runway. In Experiment 2 the test series (either RN or RRN) occurred in a gray runway about 15 min after the study series, also in a gray runway. In both experiments rats learned that the study series was the same as the test series. A hierarchical interpretation was suggested in which runway trials are organized into series, series being organized into lists.

Maintenance-Feeding Effort Affects Instrumental Performance

The effort required of rats to obtain food, employing standard maintenance-feeding procedures, can affect the effort subsequently expended in an instrumental-learning task. Rats received 43 food-rewarded runway trials followed by access to food (a) on the home-cage floor, or (b) from a hopper attached to the home-cage's wiremesh front wall. Hopper feeding involved the greater effort since the rats had to gnaw the food pellets through the wire mesh. Following 9 or 27 days of maintenance feeding, the rats were returned to the runway for one rewarded trial and 16 extinction trials. The hopper-fed rats ran faster than floor-fed rats on the rewarded test trial. In extinction, long-term maintenance feeding produced faster subsequent running times by the hopper-fed rats than the floor-fed rats. Short-term maintenance feeding, on the other hand, produced slower running times by the hopper-fed rats than the floor-fed rats. The results are consistent with previous findings of transfer of effort across behaviours and suggest that the effort required for reinforcement in the maintenance environment can systematically influence the effectiveness of various experimental treatments.

Retention of a running response following appetitive acquisition, extinction, and discrimination

In Experiment 1, hungry rats received 30 rewarded runway trials and then either extinction trials followed by retention tests or just retention tests. Different groups were tested after retention intervals of 1 min, 1, 3, or 24 h, or 30 days. Retention of extinction training was a nonmonotonic, cubic function of time for the early portion of the response chain, with good retention at 1 min and 3 h and little retention at 1 h, 24 h, or 30 days. In the latter portions of the response chain, retention of extinction decreased monotonically with time. Retention following reward-only training varied little in time, though slight losses occurred after 30 days. Experiments 2–3 differed from Experiment 1 in imposing nonchoice discrimination training (reward vs. nonreward) instead of extinction following 30 rewarded trials. After different time intervals (.017, .75, 1.25, 3, and 24 h in Experiment 1; and .017, 1, and 3 h in Experiment 2), retention tests revealed poorest discrimination at intermediate intervals in the initial portion of the response chain, i.e., a Kamin effect appeared. The deficit seemed the result of a loss of response suppression to the cue that signaled nonreward. In latter segments of the response chain, a Kamin effect tended not to appear. Implications for a number of observations and theoretical views are noted.

Resistance to extinction as a function of reinforcement schedule and amount of reinforcement

Twenty male albino rats were trained to run a straight runway on a partial reinforcement schedule. On reinforced trials a lever was introduced into the goalbox, and the subject leverpressed for sucrose on either a continuous reinforcement schedule (CRF) or on a partial reinforcement schedule (PR). On nonreinforced runway trials, the lever in the goalbox remained retracted. Upon completion of acquisition, subjects were extinguished in the runway. Results showed that subjects that received CRF on the lever were significantly more resistant to extinction than were subjects that received PR on the lever.

Effects of varying sucrose reinforcers and amobarbital sodium on positive contrast in rats

The effect of quantity and quality of reinforcement on performance change following a shift to uniform high reward was studied in four groups of rats. Twenty or 200 licks of a 5% or 20% sucrose solution constituted the four incentive conditions. Two additional subject groups were run in the high (20%–200 licks) and low (5%-20 licks) reward conditions to determine how amobarbital sodium, an emotional depressant, influences incentive shift performance. All six groups received 60 preshift runway trials (6/day), followed by 30 high reward trials. Twenty-four extinction trials contrasted drugged and normal performance relating to high and low reward Postshift positive contrast appeared in all nondrugged groups. An emotional base for positive contrast is considered.

Activity level changes preceding runway trials: An index of conditioned fear

Two experiments with hooded rats, in which activity level changes before runway trials are explored as an index of conditioned fear, are reported. Animals were dropped into a shock runway from an enclosed chamber where activity was monitored. Those that received shock in the runway showed a reliable decline in activity, significantly correlated with a reliable rise in running speed. When extinction trials were widely spaced (Exp. II), the activity-level measure accurately monitored both extinction and spontaneous recovery of fear. These results suggest the activity measure as a useful tool for investigation of fear in complex behavior.

Influence of reward magnitude on the initial nonreward effect

Two groups received 20 nonrewarded (N) runway trials followed by either 20 small-reward (2 pellets) or 20 large-reward (20 pellets) trials (Groups N-2 and N-20, respectively). Groups receiving 40 small-reward (Group 2-2) or 40 large-reward (Group 20-20) trials were also included (N = 10 rats/group). An initial nonreward effect (INE) was obtained, with Groups N-2 and N-20 being more resistant to extinction than Groups 2-2 and 20-20, respectively. The size of the INE was independent of reward magnitude, and small-reward groups were more resistant to extinction than large-reward groups.

Activity level and secondary motivation: Incentive

Activity level was monitored in the startbox before a runway trial for a group of eight rats running for food reward, and for a second group of eight rats receiving identical treatment but with no reward given. There was no evidence for an excitatory incentive response, as the groups’ activity levels did not differ during acquisition. In extinction, the previously rewarded animals were more active, suggesting a frustration effect.

Nonreward anticipated: Effects on extinction runway performance in the rat

Following a 47-day extinction procedure, the reinstatement of the cue previously associated with reward produced an immediate improvement in performance. The cue was the opportunity to traverse the alley following an “anticipated” nonrewarded runway trial. Moreover, the animals trained in this matter exhibited daily increments in performance during the initial phase of extinction testing. The results were interpreted as consistent with the notion that the difference in extinction performance of one group as compared to another does not necessarily reflect the relative “strengths” of the instrumentally acquired habits. Instead, it probably indicates the degree of similarity of the extinction testing procedure to the acquisition training condition previously associated with reinforcement for the two individual groups.

Acquisition and transfer effects of cued and noncued double alternation schedules with rats

In an attempt to establish patterning, rats were administered eight daily runway trials in a double alternation schedule with distinctive goal events in either a consistent or a varied sequence. Different magnitudes of reward differentiated the reinforced trials, whereas different lengths of confinement in the empty goal box distinguished the nonreinforced trials. During acquisition, rats given the consistent cue sequence “patterned”, whereas the group presented varied cues did not. Subsequently, the Consistent and Varied Cue Groups were subdivided and were administered for 2 days only one of the four acquisition training goal events. During the final 5 days of transfer testing, all subgroups were switched to receiving four daily trials with a second and then a third goal event. In agreement with expectations derived from stimulus aftereffects theory, performance was immediately in accord with the reinforcement contingencies previously established during acquisition training and not the goal event actually presented during testing.

Runway Performance as a Function of Magnitude of Runway Reward and Intertrial Reinforcement

Rats were trained to traverse a straight alley for either 1 or 10 food pellets as reward. Each runway trial was preceded by an intertrial reinforcement of 1 or 10 pellets. A negative contrast effect obtained and persisted throughout the 72 trials conducted. Although there was a strong suggestion of a positive contrast effect throughout training, the effect did not prove reliable. The contrast effect results were interpreted as challenging the view that with extended training ITRs become “irrelevant” to runway reward.

Effect on runway performance of reinforcement contingencies established to empty goal-box placements

In order to investigate the hypothesis that rats discriminate nonreinforced goal-box placements from runway trials and to show that such differentiation can affect resistance to extinction, animals received partial reinforcement during acquisition and placements to an unbaited goal box either ( a) positively, ( b) negatively, or ( c) randomly related to reinforced runway (R) trials. During acquisition, animals in conditions a and b ran faster on R trials than on nonreinforced runway trials. The subjects in condition c showed the greatest resistance to extinction. Reinstatement of the placement procedure after extensive extinction testing produced an immediate increment in runway performance for the animals in condition a. These results clearly indicated that rats are capable of differentiating placement events from runway trials, and that such differentiation can affect resistance to instruction.

Resistance to Extinction as a Function of the Number of Small and Large Rewarded Runway Trials

4 groups of 10 rats were trained in a runway for 0, 5, 10, or 15 small rewarded (2 pellets) trials prior to being shifted to large reward (24 pellets) for the remainder of 45 trials. Acquisition performance was slower for small than for large reward during the early trials but the groups were not different by the end of acquisition. Resistance to extinction was an increasing linear function of the number of small rewarded trials.