Approach-avoidance Conflict Behavior Research Articles

The effects of hydrocortisone and yohimbine on human behavior in approach-avoidance conflicts

RationaleBalancing approach of positive and avoidance of negative stimuli is essential when faced with approach-avoidance conflicts, e.g., situations with both positive and negative outcomes. This balance is disturbed in several mental disorders, e.g., excessive avoidance in anxiety disorders, and heightened approach in substance use disorders. Since stress is assumed to impact these disorders’ etiology and maintenance, it seems crucial to understand how stress influences behavior in approach-avoidance conflicts. Indeed, some studies suggested altered approach-avoidance behavior under acute stress, but the mechanism underlying these effects is unknown.ObjectivesInvestigate how the pharmacological manipulation of major stress mediators (cortisol and noradrenaline) influences task-based approach-avoidance conflict behavior in healthy individuals.MethodsNinety-six participants (48 women, 48 men) received either 20mg hydrocortisone, 20mg yohimbine, both, or placebo before performing a task targeting foraging under predation in a fully crossed double-blind between-subject design. Moreover, we investigated effects of gender and endogenous testosterone and estradiol levels on approach-avoidance behavior.ResultsWhile biological stress markers (cortisol concentration, alpha amylase activity) indicated successful pharmacological manipulation, behavior in approach-avoidance conflicts was not affected as expected. Although yohimbine administration affected risky foraging latency under predation, we found no main effect of hydrocortisone or their interaction on behavior. In contrast, we found gender differences for almost all behavioral outcome measures, which might be explained by differences in endogenous testosterone levels.ConclusionsThe investigated major stress mediators were not sufficient to imitate previously shown stress effects on approach-avoidance conflict behavior. We discuss potential reasons for our findings and implications for future research.

Relationship between voluntary ethanol drinking and approach-avoidance biases in the face of motivational conflict: novel sex-dependent associations in rats.

Aberrant approach-avoidance conflict processing may contribute to compulsive seeking that characterizes addiction. Exploration of the relationship between drugs of abuse and approach-avoidance behavior remains limited, especially with ethanol. To investigate the effects of voluntary ethanol consumption on approach-avoidance conflict behavior and to examine the potential approach/avoidance bias to predict drinking in male and female rats. Long-Evans rats consumed ethanol for 5 weeks under the intermittent access two-bottle choice (IA2BC) paradigm. Approach-avoidance tendencies were assessed before and after IA2BC drinking using a previously established cued approach-avoidance conflict maze task and the elevated plus maze (EPM). Female rats displayed higher consumption of and preference for ethanol than males. In the conflict task, males showed greater approach bias towards cues predicting conflict than females. In females only, a median split and regression analysis of cued-conflict preference scores revealed that the more conflict-avoidant group displayed higher intake and preference for ethanol in the first few weeks of drinking. In both sexes, ethanol drinking did not affect cued-conflict preference, but ethanol exposure led to increased time spent in the central hub in the males only. Finally, anxiety levels in EPM predicted subsequent onset of ethanol drinking in males only. Our results highlight sex and individual differences in both drinking and approach-avoidance bias in the face of cued conflict and further suggest that cued-conflict preference should be examined as a potential predictor of ethanol drinking. Ethanol exposure may also affect the timing of decision-making in the face of conflict.

Double dissociation of learned approach-avoidance conflict processing and spatial pattern separation along the dorsoventral axis of the dentate gyrus.

The ventral portion of the rodent hippocampus (HPC; anterior in primates) has been implicated in the detection and resolution of approach-avoidance conflict, which arises when an organism encounters a stimulus that predicts both positive and negative outcomes. Previous work has found differential regulation of approach-avoidance conflict behavior by the CA3 and CA1 subfields, with inhibition of ventral CA3 increasing approach toward conflicting stimuli and inhibition of the ventral CA1 potentiating avoidance. Here, we sought to extend these findings by investigating the role of the dentate gyrus (DG), the input region of the HPC, in learned approach-avoidance conflict processing in rats. Animals were first trained to acquire three different visuotactile cue-outcome associations in separate arms of a Y-maze (appetitive, aversive, and neutral). Postacquisition, they were administered a "conflict test," in which they were presented with a choice between exploring an arm in which the appetitive and aversive cues were concurrently presented (conflict stimulus), and another arm containing the neutral stimulus. GABAR-mediated inactivation of the ventral DG, but not dorsal DG, potentiated approach behavior toward the conflict stimulus, similar to the effects of ventral CA3 inactivation. In contrast, dorsal DG, but not ventral DG, inactivation was found to impair performance on a metric spatial discrimination task, which is commonly used as a test of pattern separation. The findings of this study demonstrate a robust double dissociation between the ventral and dorsal aspects of the DG, in line with previous reports of functional differences along the longitudinal axis of the HPC.

Divergent medial amygdala projections regulate approach-avoidance conflict behavior.

Avoidance of innate threats is often conflicted by motivations to engage in exploratory approach behavior. The neural pathways that mediate this approach-avoidance conflict are not well resolved. Here, we isolated a population of dopamine D1 receptor (D1R) expressing neurons within the posteroventral region of the medial amygdala (MeApv) in mice that are activated either during approach or during avoidance of an innate threat stimulus. Distinct subpopulations of MeApv-D1R neurons differentially innervate the ventromedial hypothalamus (VMH) and bed nucleus of the stria terminalis (BNST) and these projections have opposing effects on investigation or avoidance of threatening stimuli. These projections are potently modulated through opposite actions of D1R signaling that bias approach behavior. These data demonstrate divergent pathways in the MeApv that can be differentially weighted towards exploration or evasion of threats.

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.

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.

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.

An interference-reduction theory of the effects of ethanol on conflict behavior

The classic tension-reduction theory of the effects of ethanol on approach-avoidance conflict behavior involves the assumption that the drug reduces conflict by selectively weakening fear-motivated avoidance but not approach. An alternative interpretation in which alcohol is seen as reducing the capacity of the weaker of any two competitive tendencies, whether inhibitory or excitatory, to interfere with the stronger is proposed here. Data from studies of isolated avoidance gradients and from experiments on approach-avoidance and avoidance-avoidance conflicts which support an interference-reduction rather than a tension-reduction theory are reported.

Approach-avoidance conflict behavior as a result of prior exposure to a conflict situation.

(1972). Approach-Avoidance Conflict Behavior as a Result of Prior Exposure to a Conflict Situation. The Journal of General Psychology: Vol. 86, No. 1, pp. 117-130.

Approach-avoidance conflict behavior as a function of amount and spacing of prior electric shock

In a factorial study, albino rats were subjected to either six 5-sec. or 30 1-sec. electric shocks for either one or five days and were subsequently tested in an approach-avoidance conflict situation with shock used as the aversive stimulus. The effectiveness of the punishment in the conflict situation did not vary as a function of the spacing or amount of prior electric shock. However, all prior-shock groups were more sensitive to subsequent electric shock than was a no-prior-shock control group.

Effects of stimulus intensity on approach-avoidance conflict behavior

Using FR approach and conflict chains and a light whose intensity increased or decreased within the FR as a function of responding, the present experiment found stimulus intensity to affect performance only when on-trial stimuli were discriminated from off-trial stimuli by permitting nonreinforced barpressing during the intertrial interval. These findings suggest a stimulus intensity, rather than a discriminative, origin of observed inequalities in the slopes of approach and avoidance gradients.

Approach-avoidance conflict behavior as a function of prior shock stimulation

Albino rats received a series of spaced 1-sec. shocks administered in then homecages for five consecutive days, and were later tested in an approach-avoidance conflict situation with either shock or airblast. Compared to control groups the prior-shock Ss were initially less sensitive to the effects of electric shock in the conflict situation.

Approach-avoidance conflict behavior as a function of prior experience with mild or intense electric shock stimulation

Albino rats were subjected to a series of either intense (.80 ma) or mild (.25 ma) electric shock and were later tested in a conflict situation with the same level of shock serving as the aversive stimulus. Two no-prior-shock control groups were also tested in the conflict situation under either mild or intense shock. Both prior shock groups were more sensitive to subsequent shock than were their respective no-shock control groups.