bioRxiv Science⌕ Search

Biology subjects

Servonnet, A.

Publications and source records attributed to Servonnet, A..

4 recordsLinked to original sources

Optogenetic activation of basolateral amygdala projections to nucleus accumbens core promotes cue-induced expectation of reward but not instrumental pursuit of cues

Reward-associated conditioned stimuli (CS) can acquire predictive value, evoking conditioned approach behaviors that prepare animals to engage with forthcoming rewards. Such CS can also acquire conditioned reinforcing value, becoming attractive and pursued. Through their predictive and conditioned reinforcing properties, CS can promote adaptive (e.g., locating food) but also maladaptive responses (e.g., drug use). Basolateral amygdala neurons projecting to the nucleus accumbens core (BLA[->]NAc core neurons) mediate the response to appetitive CS, but the extent to which this involves effects on the predictive and/or conditioned reinforcing properties of CS is unclear. Thus, we examined the effects of optogenetic stimulation of BLA[->]NAc core neurons on conditioned approach behavior and on the instrumental pursuit of a CS, the latter a measure of conditioned reinforcement. Water-restricted, adult male rats learned that a light-tone compound cue (CS) predicts water delivery. Pairing optogenetic stimulation of BLA[->]NAc core neurons with CS presentation potentiated conditioned approach behavior, and did so even under extinction conditions, when water was omitted. This suggests that BLA[->]NAc core neurons promote cue-induced expectation of rewards. Rats also received instrumental conditioning sessions during which they could lever press for CS presentations, without water delivery. Optogenetic stimulation of BLA[->]NAc core neurons either during these instrumental test sessions or during prior CS-water conditioning did not influence lever responding for the CS. This suggests that BLA[->]NAc core neurons do not influence the conditioned reinforcing effects of CS. We conclude that BLA[->]NAc core neurons promote cue-induced control over behavior by increasing cue-triggered anticipation of rewards, without influencing cue wanting. SIGNIFICANCE STATEMENTEnvironmental cues associated with rewards guide animals toward rewards essential for survival such as food. Reward-associated cues can also evoke maladaptive responses such as in addiction. Reward cues guide behavior in two major ways. First, they evoke approach toward imminent rewards, preparing animals to engage with these rewards. Second, cues can become attractive themselves, such that animals will learn new behaviors simply to obtain them. Here we show that activation of basolateral amygdala neurons projecting to the nucleus accumbens core increases cue-induced approach to the location of reward, without influencing the pursuit of reward cues. Thus, these amygdala-to-accumbens neurons promote cue-induced expectation of reward, without changing the attractiveness of cues.

neuroscience↗

Metabotropic group II glutamate receptors in the basolateral amygdala mediate cue-triggered increases in incentive motivation

RationaleReward-associated cues can trigger incentive motivation for reward and invigorate reward-seeking behaviour via Pavlovian-to-instrumental transfer (PIT). Glutamate signaling within the basolateral amygdala (BLA) modulates cue-triggered increases in incentive motivation. However, the role of BLA metabotropic group II glutamate (mGlu2/3) receptors is largely unknown. ObjectivesIn Experiment 1, we characterized cue-triggered increases in incentive motivation for water reward using the PIT paradigm. In Experiment 2, we assessed the influence of intra-BLA microinjections of the mGlu2/3 receptor agonist LY379268 on this effect. MethodsWater-restricted male Sprague-Dawley rats learned to press a lever for water. Separately, they learned to associate one of two auditory cues with free water. On test days, rats could lever press under extinction conditions (no water), with intermittent, non-contingent CS+ and CS- presentations. In Experiment 1, rats were tested under baseline conditions. In Experiment 2, rats received intra-BLA microinjections of LY379268 (0, 3 and 6 g/hemisphere) before testing. ResultsAcross experiments, CS+, but not CS- presentations increased water-associated lever pressing during testing, even though responding was reinforced neither by water nor the CS+. Intra-BLA LY379268 abolished both CS+ potentiated pressing on the water-associated lever and CS+ evoked conditioned approach to the site of water delivery. LY379268 did not influence locomotion or instrumental and Pavlovian response rates during intervals between CS presentations or during the CS-, indicating no motor effects. ConclusionsmGlu2/3 receptor activity in the BLA mediates CS-triggered potentiation of incentive motivation for reward, suppressing both CS-induced increases in instrumental pursuit of the reward and anticipatory approach behaviour.

neuroscience↗

Where and how does d-amphetamine act to reveal antipsychotic-induced dopamine supersensitivity in rats?

Antipsychotic treatment can produce a dopamine-supersensitive state, potentiating the response to dopamine receptor stimulation. In both schizophrenia patients and rats, this is linked to tolerance to ongoing antipsychotic treatment. In rodents, dopamine supersensitivity is often confirmed by an exaggerated psychomotor response to d-amphetamine after discontinuation of antipsychotic exposure. Here we examined in rats the dopaminergic mechanisms mediating this enhanced behavioural response, as this could uncover pathophysiological processes underlying the expression of antipsychotic-evoked dopamine supersensitivity. Rats received 0.5 mg/kg/day haloperidol via osmotic minipump for 2 weeks, before treatment was discontinued. After cessation of antipsychotic treatment, rats showed a supersensitive psychomotor response to the D2 agonist quinpirole, but not to the D1 partial agonist SKF38393 or the dopamine reuptake blocker GBR12783. Furthermore, acute D1 receptor blockade (using SCH39166) decreased the exaggerated psychomotor response to d-amphetamine in haloperidol-pretreated rats, whereas acute D2 receptor blockade (using sulpiride) enhanced it. Thus, after discontinuation of antipsychotic treatment, D1- and D2-mediated transmission differentially modulate the expression of a supersensitive response to d-amphetamine. This supersensitive behavioural response was accompanied by enhanced GSK3{beta} activity and suppressed ERK1/2 activity in the nucleus accumbens (but not caudate-putamen), suggesting increased mesolimbic D2 transmission. Finally, after discontinuing haloperidol treatment, neither increasing ventral midbrain dopamine impulse flow nor infusing d-amphetamine into the cerebral ventricles triggered the expression of already established antipsychotic-evoked dopamine supersensitivity, suggesting that peripheral effects are required. Thus, while dopamine receptor-mediated signalling regulates the expression of antipsychotic-evoked dopamine supersensitivity, a simple increase in central dopamine neurotransmission is insufficient to trigger this supersensitivity. HIGHLIGHTSO_LIAntipsychotic exposure can lead to a state of dopamine (DA) supersensitivity C_LIO_LIIn rats, this DA supersensitivity potentiates d-amphetamine-induced locomotion C_LIO_LIWe report that D2 transmission promotes DA supersensitivity and D1 transmission tempers it C_LIO_LID-amphetamines central effects are also insufficient to reveal DA supersensitivity C_LI

pharmacology and toxicology↗

The basolateral nucleus of the amygdala regulates both the predictive and incentive motivational properties of reward cues

Reward-associated stimuli can acquire both predictive and incentive motivational properties. These conditioned stimuli (CS) can then guide reward-seeking behaviour in adaptive (e.g., locating food) and maladaptive (e.g., binge eating) ways. The basolateral amygdala (BLA) contributes to learning of the predictive value of CS, but less is known about BLA contributions to the incentive motivational properties of appetitive CS. Here we studied the influence of BLA neuron activity on both the predictive and incentive motivational effects of CS. Water-restricted male rats learned to associate a light-tone cue (CS) with water delivery into a port. We assessed the predictive value to the CS by measuring CS-evoked port entries during Pavlovian conditioning. We assessed CS-evoked incentive motivation by measuring lever-pressing for the CS during instrumental responding sessions. During Pavlovian conditioning, we paired CS presentations with photo-stimulation of channelrhodopsin-2 (ChR2)-expressing BLA neurons. This potentiated CS-evoked port entries during conditioning, but suppressed subsequent lever-pressing for the CS. This indicates increased conditioned responding to the CS, but an apparent decrease in incentive motivation for that CS. However, in rats previously naive to photo-stimulation, pairing BLA-ChR2 stimulations during lever-pressing for the CS intensified responding, indicating enhanced motivation for the CS. Rats did not self-administer BLA-ChR2 stimulations, suggesting that BLA activation does not carry a primary reward signal. Lastly, intra-BLA infusions of d-amphetamine also intensified lever-pressing for the CS. These converging findings suggest that BLA mediated-activity enhances both the predictive and incentive motivational properties of CS, allowing BLA-dependent circuits to guide behaviour in the presence of reward-associated cues.\n\nSIGNIFICANCE STATEMENTCues paired with rewards can guide animals to valuable resources such as food. Cues can also promote dysfunctional reward-seeking behaviour, as in over-eating. Reward-paired cues influence reward seeking through two major mechanisms. First, reward-paired cues are predictive and thus evoke anticipation of future rewards. Second, reward-paired cues are powerful motivators and they can evoke pursuit in their own right. Here we show that increasing neural activity in the basolateral amygdala enhances both the predictive and motivational effects of reward-paired cues. The basolateral amygdala therefore facilitates cue-induced control over behaviour by both increasing anticipation for impending rewards and making reward cues more attractive.

animal behavior and cognition↗