Straight Alley Research Articles

Hippocampal motor memory network reorganization depends on familiarity, not time.

There is debate as to whether a time-dependent transformation of the episodic-like memory network is observed for nonepisodic tasks, including procedural motor memory. To determine how motor memory networks reorganize with time and practice, mice performed a motor task in a straight alley maze for 1 d (recent), 20 d of continuous training (continuous), or testing 20 d after the original training (remote), and then regional c-Fos expression was assessed. Elevated hippocampal c-Fos accompanied remote, but not continuous, motor task retrieval after 20 d, suggesting that the hippocampus remains engaged for nonhabitual remote motor memory retrieval.

Tribute to E. J. Capaldi: Celebration of a Psychological Scientist

Abstract E. J. (John) Capaldi (1928–2020) made numerous contributions to experimental psychology in his long career at the University of Texas at Austin and Purdue University. He was a pioneer in the area of animal learning and cognition, known for his sequential theory of partial reinforcement extinction effects. His research in this area and in memory and counting phenomena was conducted for the most part with rats running in straight alley mazes under various sequences of trial outcomes (e.g., reward, nonreward, variations in reward size). John's other interests included the sequential theory applied to Pavlovian conditioning, evolutionary theory, and psychology of science. More generally, John was a scientist to the core who served as a role model to those who knew him. His career centered on the values of science and rigorous critical thinking based in empirical data, coupled with a curiosity and openness to different and new ideas in psychology.

Conflict Test Battery for Studying the Act of Facing Threats in Pursuit of Rewards.

Survival depends on the ability of animals to avoid threats and approach rewards. Traditionally, these two opposing motivational systems have been studied separately. In nature, however, they regularly compete for the control of behavior. When threat- and reward-eliciting stimuli (learned or unlearned) occur simultaneously, a motivational conflict emerges that challenges individuals to weigh available options and execute a single behavioral response (avoid or approach). Most previous animal models using approach/avoidance conflicts have often focused on the ability to avoid threats by forgoing or delaying the opportunity to obtain rewards. In contrast, behavioral tasks designed to capitalize on the ability to actively choose to execute approach behaviors despite threats are scarce. Thus, we developed a behavioral test battery composed of three conflict tasks to directly study rats confronting threats to obtain rewards guided by innate and conditioned cues. One conflict task involves crossing a potentially electrified grid to obtain food on the opposite end of a straight alley, the second task is based on the step-down threat avoidance paradigm, and the third one is a modified version of the open field test. We used diazepam to pharmacologically validate conflict behaviors in our tasks. We found that, regardless of whether competing stimuli were conditioned or innate, a low diazepam dose decreased risk assessment and facilitated taking action to obtain rewards in the face of threats during conflict, without affecting choice behavior when there was no conflict involved. Using this pharmacologically validated test battery of ethologically designed innate/learned conflict tasks could help understand the fundamental brain mechanisms underlying the ability to confront threats to achieve goals.

Use of cognitive bias as a welfare tool in poultry.

In human psychology, the link between cognition and emotions is broadly accepted. However, the idea of using the interaction between cognition and emotions as a tool for a better understanding of animal emotions or for welfare assessment is relatively new. The first avian species used in cognitive bias tests was the European starling followed by the domestic chicken and other species. The most frequently used paradigm is the affect-induced judgment bias. There are many variations of the judgment bias tests in birds. The test itself is preceded by discrimination training. Discrimination tasks vary from visual cue discrimination, discrimination of time intervals to spatial location discrimination. During the discrimination training, birds flip or do not flip the lids of the food dishes, and their latency to approach the cues in a straight alley maze, in a two-choice arena, or different locations in spatial judgment task arena are measured. Alternately, the birds fulfill operant tasks in a Skinner box. Before or after the discrimination training phase, birds are subjected to manipulations that are hypothesized to induce positive or negative emotional states. In the last stage, birds are subjected to judgment bias tests. The assumption is that animals in a negative affective state would more likely respond to ambiguous cues, as if they predict the negative event, than animals in a more positive state. However, the results of some avian studies are inconsistent, particularly those studying the effect of environmental enrichment. In starlings, each of the three studies has supplied conflicting results. In poultry, none of the four studies demonstrated a positive effect of environmental enrichment on emotional states. Only the study using unpredictable stressors in combination with environmental complexity showed that animals kept in a more complex environment are more optimistic. Manipulation of the social environment seems to be more effective in judgment bias induction. Conflicting results could be attributable to the design of the tests, the manner of affect induction, or the data analysis. Further optimization and validation of avian cognitive bias tests could help to avoid problems such as the loss of ambiguity. New methods of attention and memory bias testing are promising. However, regardless of the abovementioned complications, a cognitive bias paradigm is a valuable tool, which can help us better understand avian emotions and assess poultry welfare.

Methamphetamine self-administration in a runway model of drug-seeking behavior in male rats

Cocaine administration has been shown to produce immediate positive (rewarding) and subsequent negative (anxiogenic) effects in humans and animals. These dual and opposing affective responses have been more difficult to demonstrate with administration of methamphetamine (meth). While animal studies have reliably demonstrated the positive reinforcing effects of the drug, reports of negative aftereffects following acute exposure have been few in number and contradictory in nature. The current research was devised to assess the effects of acute meth using a runway model of self-administration that is uniquely sensitive to both the positive and negative effects of a drug reinforcer in the same animal on the same trial. Male rats were allowed to traverse a straight alley once a day for 16 consecutive days/trials where entry into the goal box resulted in a single IV injection of meth (0.25, 0.5 or 1.0 mg/kg/inj.). The chosen doses were confirmed to be psychoactive as they produced dose-dependent increases in motoric/locomotor activation in these same subjects. The results demonstrated a U-shaped dose-response curve for the reinforcing effects of meth in that the intermediate dose group (0.5 mg/kg) produced the strongest approach behavior in the runway. Unlike other psychomotor stimulants, like cocaine, animals running for IV meth exhibited no evidence of any significant approach-avoidance behaviors reflective of the drug's negative anxiogenic effects. These results suggest that the abuse potential for meth is likely higher than for other shorter-acting psychomotor stimulants and reaffirms the utility of the runway procedure as a screen for a substance's abuse potential.

Repeated Cocaine Exposure Attenuates the Desire to Actively Avoid: A Novel Active Avoidance Runway Task.

Drug addiction is a disorder in which drug seeking persists despite aversive consequences. While it is well documented in animal models of drug sensitization that repeated drug exposure enhances positive incentive motivation for drug and natural reinforcers, its effect on negative incentive motivation, defined here as the motivation to avoid a cued aversive outcome, remains an open question. In the present study, we designed a novel active avoidance (AA) runway paradigm to assess the effects of repeated cocaine exposure on the motivation to avoid an aversive outcome. Cocaine and saline pre-exposed rats were first trained to perform a conditioned AA lever press response to prevent the occurrence of foot shock administrations. The rats were subsequently tested in a runway apparatus, wherein they were required to traverse the length of a straight alley maze to reach the lever and emit a conditioned AA response. Run times were measured as an indication of negative incentive motivation. Cocaine pre-exposed rats demonstrated longer latencies to emit the conditioned AA response but showed no differences in latency to initiate runway behavior, nor in their acquisition of the AA response compared to the saline pre-exposed controls. Subsequent testing in an elevated plus maze revealed no differences in the expression of anxiety in cocaine pre-exposed rats compared to saline pre-exposed controls. Our results indicate that prior repeated cocaine exposure attenuated cued negative incentive motivation, which suggests that drug addiction may be attributable to a decrease in motivation to avoid aversive consequences associated with drug use.

Differential effects of neural inactivation of the dorsolateral striatum on response and latent extinction.

The present study examined the role of the dorsolateral striatum (DLS) in extinction behavior. Male Long-Evans rats were initially trained on the straight alley maze, in which they were reinforced to traverse a straight runway and retrieve food reward at the opposite end of the maze. After initial acquisition, animals were given extinction training using 1 of 2 distinct protocols: response extinction or latent extinction. For response extinction, the animal was released from the same starting position and had the opportunity to perform the originally reinforced approach response to the goal end of the maze, which no longer contained food. For latent extinction, the animal was confined to the original goal location without food, allowing the animal to form a new cognitive expectation (i.e., that the goal location is no longer reinforced). Immediately before response or latent extinction training, animals received bilateral intra-DLS administration of the sodium channel blocker bupivacaine or control injections of physiological saline. Results indicated that neural inactivation of the DLS with bupivacaine impaired response extinction, but did not influence latent extinction. The dissociation observed indicates that the DLS selectively mediates extinction mechanisms involving suppression of the original response, as opposed to cognitive mechanisms involving a change in expectation. (PsycINFO Database Record

Attenuation of the anxiogenic effects of cocaine by 5-HT1B autoreceptor stimulation in the bed nucleus of the stria terminalis of rats.

Cocaine produces significant aversive/anxiogenic actions whose underlying neurobiology remains unclear. A possible substrate contributing to these actions is the serotonergic (5-HT) pathway projecting from the dorsal raphé (DRN) to regions of the extended amygdala, including the bed nucleus of the stria terminalis (BNST) which have been implicated in the production of anxiogenic states. The present study examined the contribution of 5-HT signaling within the BNST to the anxiogenic effects of cocaine as measured in a runway model of drug self-administration. Male Sprague-Dawley rats were fitted with bilateral infusion cannula aimed at the BNST and then trained to traverse a straight alley once a day for a single 1mg/kg i.v. cocaine infusion delivered upon goal-box entry on each of 16 consecutive days/trials. Intracranial infusions of CP 94,253 (0, 0.25, 0.5, or 1.0μg/side) were administered to inhibit local 5-HT release via activation of 5-HT1B autoreceptors. To confirm receptor specificity, the effects of this treatment were then challenged by co-administration of the selective 5-HT1B antagonist NAS-181. Intra-BNST infusions of the 5-HT1B autoreceptor agonist attenuated the anxiogenic effects of cocaine as reflected by a decrease in runway approach-avoidance conflict behavior. This effect was reversed by the 5-HT1B antagonist. Neither start latencies (a measure of the subject's motivation to seek cocaine) nor spontaneous locomotor activity (an index of motoric capacity) were altered by either treatment. Inhibition of 5-HT1B signaling within the BNST selectively attenuated the anxiogenic effects of cocaine, while leaving unaffected the positive incentive properties of the drug.

Pharmacological modulation of lateral habenular dopamine D2 receptors alters the anxiogenic response to cocaine in a runway model of drug self-administration

Cocaine has long been known to produce an initial “high” followed by an aversive/anxiogenic “crash”. While much is known about the neurobiology of cocaine’s positive/rewarding effects, the mechanisms that give rise to the drug’s negative/anxiogenic actions remain unclear. Recent research has implicated the lateral habenula (LHb) in the encoding of aversive events including the anxiogenic response to cocaine. Of particular interest in this regard are the reciprocal connections between the LHb and the ventral tegmental area (VTA). VTA-DA neurons innervate different subsets of LHb cells that in turn feedback upon and modulate VTA neuronal activity. Here we examined the impact of D2 receptor activation and inhibition on the anxiogenic response to cocaine using a runway model of self-administration that is sensitive to the dual and opposing effects of the drug. Male rats ran a straight alley for IV cocaine (1.0mg/kg) following bilateral intra-LHb infusions of the D2 receptor antagonist, cis-flupenthixol (0, 7.5 or 15μg/side) or the D2 agonist, sumanirole (0, 5 or 10μg/side). Vehicle-pretreated controls developed approach-avoidance conflict behaviors about goal-box entry reflective of the dual positive and negative effects of cocaine. These behaviors were significantly diminished during LHb-D2 receptor antagonism and increased by the LHb D2 receptor agonist. These results demonstrate that activity at the D2 receptor in the lateral habenula serves to modulate the anxiogenic response to cocaine.

Incentive loss and hippocampal gene expression in inbred Roman high- (RHA-I) and Roman low- (RLA-I) avoidance rats

Two recent microarray and qRT-PCR studies showed that inbred Roman high- (RHA-I, low anxiety and frustration vulnerability) and low-avoidance (RLA-I, high anxiety and frustration vulnerability) rats, psychogenetically selected on the basis of their divergence in two-way avoidance performance, differed in basal whole-brain and hippocampal expression of genes related to neurotransmission, emotion, stress, aversive learning, and drug seeking behavior. We have extended these studies by analyzing strain differences in hippocampal gene expression following a frustrative experience involving reward downshift, i.e. instrumental successive negative contrast (iSNC), a phenomenon in which the sudden reduction of an expected reward induces frustration/anxiety. Food-deprived male Roman rats were exposed to a reduction in the amount of solid food presented in the goal of a straight alley (from 12 pellets in “training” trials – i.e. preshift trials- to 2 pellets in “frustration testing” trials – i.e. postshift trials-). The iSNC effect, as measured by response latencies in the “postshift” trials, appeared only in RLA-I rats (i.e. higher response latencies in the 12-2 RLA-I group as compared to the 2-2 RLA-I control group in postshift trials). Two and a half hours after the “postshift” behavioral test, hippocampi were removed and stored (−80°C) until analysis. Microarray analysis of these hippocampi showed that four differentially-expressed, and qRT-PCR-validated genes (TAAR2, THAP1, PKD2L1, NANOS), have relevance for brain function and behavior, including schizophrenia, depression, anxiety, and drug addiction, thus showing the usefulness of Roman strains as a genetic model for research on the neurogenetic basis of frustration.

Extinction makes conditioning time-dependent.

Two experiments explored whether forgetting of an association depended on previous extinction of a different association in rats. Experiment 1 found that when rats were conditioned and extinguished with flavor X, a subsequently acquired conditioned aversion to flavor Y was reduced by a 19-day retention interval, something that did not occur when X and the US were initially presented unpaired. Experiment 2 found that when rats received training and extinction in one of two tasks (conditioned aversion to sucrose in Experiment 2a, and running for water in a straight alley in Experiment 2b), subsequent learning of the alternative task was partially forgotten over the 19-day retention interval. These results are similar to those previously found when manipulating physical and conceptual contexts in rats and humans, respectively, and suggest that the passage of time may play a role similar to the one played by the change in physical or conceptual contexts on information retrieval.

The effect of partial reinforcement on instrumental successive negative contrast in inbred Roman High- (RHA-I) and Low- (RLA-I) Avoidance rats

Frustration is an emotional response that can be induced by the sudden devaluation of a reinforcer in the presence of greater reinforcement expectancies (e.g. instrumental successive negative contrast, iSNC). This emotional response seems to be similar to anxiety and can be attenuated by previous experiences of reward loss (e.g. partial reinforcement, PR, as opposed to continuous reinforcement, CR). In this study we used iSNC and PR procedures in order to compare the performance of two strains of rats psychogenetically selected on the basis of their emotional reactivity: the inbred Roman High- (RHA-I, low anxiety) and Low- (RLA-I, high anxiety) Avoidance rats. Animals were exposed to a straight alley, where they were changed from 12 pellets in the preshift phase (presented in 100% of trials—CR vs. 50% of trials—PR) to 2 pellets in the postshift phase, or exposed to 2 pellets throughout the training. The results indicated that the iSNC only appeared in RLA-I rats exposed to CR, as opposed to RLA-I animals exposed to PR and to RHA-I rats exposed to PR or CR. These data seem to support the implication of emotional responses in both iSNC and PR situations, and indicate that the behavioral reactivity to reward loss experiences is modulated by genetic variables.

One day of motor training with amphetamine impairs motor recovery following spinal cord injury

It has previously been reported that a single dose of amphetamine paired with training on a beam walking task can enhance locomotor recovery following brain injury (Feeney et al., 1982). Here, we investigated whether this same drug/training regimen could enhance functional recovery following either thoracic (T9) or cervical (C5) spinal cord injury. Different groups of female Sprague–Dawley rats were trained on a beam walking task, and in a straight alley for assessment of hindlimb locomotor recovery using the BBB locomotor scale. For rats that received C5 hemisections, forelimb grip strength was assessed using a grip strength meter. Three separate experiments assessed the consequences of training rats on the beam walking task 24h following a thoracic lateral hemisection with administration of either amphetamine or saline. Beginning 1h following drug administration, rats either received additional testing/retraining on the beam hourly for 6h, or they were returned to their home cages without further testing/retraining. Rats with thoracic spinal cord injuries that received amphetamine in conjunction with testing/retraining on the beam at 1day post injury (DPI) exhibited significantly impaired recovery on the beam walking task and BBB. Rats with cervical spinal cord injuries that received training with amphetamine also exhibited significant impairments in beam walking and locomotion, as well as impairments in gripping and reaching abilities. Even when administered at 14DPI, the drug/training regimen significantly impaired reaching ability in cervical spinal cord injured rats. Impairments were not seen in rats that received amphetamine without training. Histological analyses revealed that rats that received training with amphetamine had significantly larger lesions than saline controls. These data indicate that an amphetamine/training regimen that improves recovery after cortical injury has the opposite effect of impairing recovery following spinal cord injury because early training with amphetamine increases lesion severity.

Weakening of negative relative to positive associations with cocaine-paired cues contributes to cue-induced responding after drug removal

Cocaine has been shown to have initial positive (euphoric) and delayed negative (anxiogenic) effects in both humans and animals. Cocaine-paired cues are consequently imbued with mixed positive and negative associations. The current study examines the relative roles of these dual associations in the enhanced drug-seeking observed upon presentation of cocaine-paired cues. Rats ran a straight alley once/day for a single i.v. injection of cocaine (1.0mg/kg/inj) in the presence of a distinctive olfactory cue (scented cotton swabs placed under the apparatus). An alternate scent was presented in a separate cage 2-h prior to runway testing. After 15 trials/days, the scents and cocaine reinforcer were removed and a series of extinction trials (lasting for 1 or 3weeks) was initiated. Immediately following extinction, runway responding was tested during a single trial in the presence of the cocaine-paired or non-paired cue. As previously reported, while subjects initiated responding faster over trials (reduced latencies to leave the start box), they exhibited a progressive increase in approach–avoidance conflict behavior (“retreats”) regarding goal-box entry, reflecting cocaine's dual positive+negative effects. Once established, retreat behaviors persisted over the course of 1 or 3 weeksdays of extinction. However, both run times and retreats decreased in response to presentation of the cocaine-paired but not the non-paired scent. These data suggest that, after reinforcer removal, cue-induced cocaine-seeking stems in part from a reduction in approach–avoidance conflict; i.e., a greater weakening of the negative relative to the positive associations that animals form with cocaine-paired stimuli.

Pharmacological reversal of cognitive bias in the chick anxiety-depression model

Cognitive bias presents in clinical populations where anxious individuals adopt a more pessimistic interpretation of ambiguous aversive stimuli and depressed individuals adopt both a more pessimistic interpretation of ambiguous aversive stimuli and a less optimistic interpretation of ambiguous appetitive stimuli. These biases have been reversed by anxiolytics and antidepressants. In the current study, chicks exposed to an isolation stressor of 5-min to induce an anxiety-like state or 60-min to induce a depressive-like state were tested in a straight alley maze to a series of morphed ambiguous appetitive (chick silhouette) to aversive (owl silhouette) cues. Chicks in the depression-like state displayed more pessimistic-like and less optimistic-like approach behavior to ambiguous aversive and appetitive cues, respectively. Both forms of cognitive bias were reversed by 15.0 mg/kg imipramine. Chicks in anxiety-like state displayed more pessimistic-like approach behavior under the ambiguous aversive stimulus cues. However, 0.10 mg/kg clonidine produced modest sedation and thus, was ineffective at reversing this bias. The observation that cognitive biases of more pessimism and less optimism can be reversed in the depression-like phase by imipramine adds to the validity of the chick anxiety–depression model as a neuropsychiatric simulation.This article is part of a Special Issue entitled ‘Anxiety and Depression’.

Effects of lidocaine-induced inactivation of the bed nucleus of the stria terminalis, the central or the basolateral nucleus of the amygdala on the opponent-process actions of self-administered cocaine in rats

In addition to its rewarding actions, cocaine has profound negative effects that are unmasked as the rewarding impact of the drug fades. While much is known about the neurobiology of cocaine reward, the mechanisms underlying the negative actions of the drug remain unclear. The current study investigates the role of three brain regions each implicated in the modulation of negative affective states-the bed nucleus of the stria terminalis (BNST), the central (CeA), and the basolateral (BLA) nucleus of the amygdala. The dual actions of cocaine were assessed using a runway self-administration procedure in which rats exhibit both approach to and avoidance of a goal box associated with cocaine administration (retreat behaviors). Here, rats ran a straight alley once/day for i.v. cocaine (1.0mg/kg/injection) over 14days during which the BNST, CeA, or BLA was inactivated via bilateral intracranial infusions of lidocaine (0 or 20μg/0.5μl/side) administered 15min prior to testing. The impact of lidocaine on spontaneous locomotor activity was also assessed to rule out nonspecific actions of the treatments. Control animals running for cocaine developed the expected pattern of approach-avoidance retreat behavior. Inactivation of the BNST attenuated such behavior, BLA inactivation had no appreciable effects, and CeA inactivation produced intermediate and more variable results. Locomotor activity was unaffected by any of the treatments. These data suggest that the BNST and to a lesser extent the CeA, but not the BLA, play a role in mediating the opponent-process actions of self-administered cocaine.

Sex and estrous cycle differences in cocaine‐induced approach‐avoidance conflict

Human and animal research indicates that females may have a higher biological propensity for cocaine abuse than do males. Furthermore, reproductive status modulates the subjective effects of cocaine in women and self-administration rates in rats. Despite the attention that has been given to the modulation of appetitive responses by reproductive status and the well-known mixed positive and negative subjective effects of cocaine, it is unknown if similar effects are observed on aversive responses to cocaine. The present study examines the impact of sex and estrous cycle on approach-avoidance behavior for cocaine as measured in the runway self-administration model. Male and freely cycling female Sprague Dawley rats were trained to traverse a straight alley for single daily injections of 1.0 mg/kg intravenous cocaine over 21 trials. Relative to males, females had significantly longer start latencies but significantly faster approach and shorter run times during the first week of training. Further, estrus females displayed significantly fewer approach-avoidance retreats across all sessions relative to non-estrus females. These results suggest that females initially exhibit greater motivation for cocaine (faster approach) than do males and that the drug's anxiogenic properties have a reduced impact on the motivation to seek cocaine (fewer retreats) in females during the estrus phase relative to other reproductive phases. These findings indicate that both sex and reproductive status contribute to the motivation for cocaine and that sex differences in addiction vulnerability may be attributable in part to differences in the motivational impact of both the appetitive and aversive properties of cocaine.

Cognitive bias in the chick anxiety–depression model

Cognitive bias is a phenomenon that presents in clinical populations where anxious individuals tend to adopt a more pessimistic-like interpretation of ambiguous aversive stimuli whereas depressed individuals tend to adopt a less optimistic-like interpretation of ambiguous appetitive stimuli. To further validate the chick anxiety–depression model as a neuropsychiatric simulation we sought to quantify this cognitive endophenotype. Chicks exposed to an isolation stressor of 5m to induce an anxiety-like or 60m to induce a depressive-like state were then tested in a straight alley maze to a series of morphed ambiguous appetitive (chick silhouette) to aversive (owl silhouette) cues. In non-isolated controls, runway start and goal latencies generally increased as a function of greater amounts of aversive characteristics in the cues. In chicks in the anxiety-like state, runway latencies were increased to aversive ambiguous cues, reflecting more pessimistic-like behavior. In chicks in the depression-like state, runway latencies were increased to both aversive and appetitive ambiguous cues, reflecting more pessimistic-like and less optimistic-like behavior, respectively.

Inactivation of the dorsal raphé nucleus reduces the anxiogenic response of rats running an alley for intravenous cocaine

Rats traversing a straight alley once a day for delivery of a single i.v. injection of cocaine develop over trials an ambivalence about entering the goal box. This ambivalence is characterized by the increasing occurrence of “retreat behaviors” where animals leave the start box and run quickly to the goal box, but then stop at the entry point and “retreat” back toward the start box. This unique pattern of retreat behavior has been shown to reflect a form of “approach–avoidance conflict” that stems from the animals' concurrent positive (cocaine reward) and negative (cocaine-induced anxiety) associations with the goal box. Cocaine blocks reuptake of the serotonergic (5-HT) transporter and serotonin has been implicated in the modulation of anxiety. It was therefore of interest to determine whether inactivation of the serotonergic cell bodies residing in the dorsal raphé nucleus (DRN) and projecting to brain areas critical for the modulation of anxiety, would alter the anxiogenic state exhibited by rats running an alley for single daily i.v. injections of 1.0 mg/kg cocaine. Reversible inactivation of the DRN was accomplished by intracranial application of a mixed solution of the GABA agonists baclofen and muscimol. While DRN inactivation had no impact on the subjects' motivation to initiate responding (i.e., latencies to leave the start box were unaffected) it reliably reduced the frequency of approach–avoidance retreat behaviors (conflict behavior). These data suggest that inactivation of the dorsal raphé reduces the conflict/anxiety otherwise present in experienced cocaine-seeking animals.

Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine

RationaleEvidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers.ObjectiveThe current study was therefore devised to test the hypothesis that differences in the animals’ responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of prior cocaine and heroin runway self-administration.MethodsRats ran a straight alley for single intravenous injections of either heroin (0.1 mg/kg/inj) or cocaine (1.0 mg/kg/inj) each paired with a distinct olfactory cue. Animals experienced 15 trials with each drug reinforcer in a counterbalanced manner. Start latencies, run times, and retreat behaviors (a form of approach-avoidance conflict) provided behavioral indices of the subjects’ motivation to seek the reinforcer on each trial. Responsiveness to each drug-paired cue was assessed after 7, 14, or 21 days of non-reinforced extinction trials. Other animals underwent conditioned place preference (CPP) testing to ensure that the two drug reinforcers were capable of producing drug–cue associations.ResultsWhile both drugs produced comparable CPPs, heroin served as a stronger incentive stimulus in the runway as evidenced by faster start and run times and fewer retreats. In contrast, cocaine- but not heroin-paired cues produced increases in drug-seeking behavior during subsequent extinction trials.ConclusionsThe subjects’ responsiveness to drug-paired cues during extinction was not predicted by differences in the motivation to seek heroin versus cocaine during prior drug self-administration.