The role of the dopamine D1 receptor in anticipatory pleasure and social play.

Social play is a highly rewarding activity seen across mammalian species that is vital for neurobehavioural development. Dysfunctions in social play are seen across psychiatric and neurodevelopmental disorders positing the importance of understanding the neurobiological mechanisms underlying social play. A multitude of neurotransmitter systems have been implicated in social play, with the present study focused on the role of dopamine, specifically the dopamine D1 receptor.

Dopamine D1 receptor and effort-based decision making in rats: The moderating effect of sex.

Dopamine is a modulating factor in effort-based decision-making, and emerging evidence from pharmacological research suggests that the dopamine D1 receptor is the primary regulator. Given the limited selectivity of pharmacological tools, we further explored this hypothesis using dopamine D1 mutant (DAD1) rats which have a specific genetic reduction in functional D1 receptors. Moreover, given the strong focus on males in neuroscience research in general and in the role of D1 receptors in effort-based learning, we compared both sexes in the present study.

The role of dopamine D1 receptors in MDMA-induced memory impairments.

(±) 3,4-Methylenedioxymethamphetamine (MDMA) is a recreationally abused psychostimulant that impairs memory performance. This effect is often attributed to a working memory impairment resulting from compromised serotonin systems. However, recent evidence from non-human animal experimental studies suggests that acute MDMA may indirectly impair memory performance through overstimulation of dopamine (DA) D1 receptors, which increases perseverative responding during memory tasks.

A genetic deletion of the serotonin transporter differentially influences the behavioural effects of MDMA.

Background: While (±)-3,4-methylenedioxymethamphetamine (MDMA) primarily induces serotonin release, it also affects dopamine and noradrenaline transmission. It is, however, unclear what role each of these neurotransmitters play in the behavioural profile of MDMA.

Methods: In this study we used the drug discrimination (DD) and the acoustic startle (ASR) paradigms to examine the behaviour of rats with and without a genetic deletion of the serotonin transporter SERT (SERT and SERT rats).

Generalization of serotonin and dopamine ligands to the discriminative stimulus effects of different doses of ±3,4-methylenedioxymethamphetamine.

Studies that have attributed the discriminative stimulus effects of ±3,4-methylenedioxymethamphetamine (MDMA) to serotonergic mechanisms typically use a relatively low training dose of 1.5 mg/kg. The role of serotonin in the discriminative stimulus effects of higher doses of MDMA is, however, unknown.

Differential effects of 3,4-methylenedioxymethamphetamine, methamphetamine, meta-Chlorophenylpiperazine, and scopolamine on behavioral repetition versus variation in rats.

Acute administration of drugs of abuse, such as MDMA and methamphetamine, disrupts performance on many operant tasks, for example, those used to study memory. This might occur in part because drugs make behavior, in general, more repetitive or more variable, or because they produce a more global disruption to performance. The current study explored this across two experiments by employing Neuringer's 'reinforced variability' procedure.

The effect of MDMA on sensitivity to reinforcement rate.

Administration of (±)3,4-methylenedioxymethamphetamine (MDMA) causes memory errors by increasing proactive interference. This might occur because MDMA alters sensitivity to reinforcement. The current 2 experiments investigated this directly by assessing the acute (Experiment 1) and chronic (Experiment 2) effects of MDMA on sensitivity to reinforcement.

The effect of reinforcer magnitude on probability and delay discounting of experienced outcomes in a computer game task in humans.

Delay and uncertainty of receipt both reduce the subjective value of reinforcers. Delay has a greater impact on the subjective value of smaller reinforcers than of larger ones while the reverse is true for uncertainty. We investigated the effect of reinforcer magnitude on discounting of delayed and uncertain reinforcers using a novel approach: embedding relevant choices within a computer game.

The disruptive effects of methamphetamine on delayed-matching-to-sample performance reflect proactive interference and are reduced by SCH23390.

Different drugs produce different patterns of impairment on delayed matching-to-sample tasks. For example, (+/-)3,4-methylenedioxymethamphetamine (MDMA) produces an increase in proactive interference. That is, subjects are less accurate when they are required to make a response different to the one they made on the immediately previous trial.

A 3-lever discrimination procedure reveals differences in the subjective effects of low and high doses of MDMA.

Drug discrimination studies have suggested that the subjective effects of low doses of (±)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have primarily examined responses to doses that do not produce substantial increases in extracellular dopamine. The present study determined whether doses of MDMA that produce increases in synaptic dopamine would also produce subjective effects that were more like AMPH and were sensitive to pharmacological manipulation of D1-like receptors.

Whatever gave you that idea? False memories following equivalence training: a behavioral account of the misinformation effect.

The misinformation effect is a term used in the cognitive psychological literature to describe both experimental and real-world instances in which misleading information is incorporated into an account of an historical event. In many real-world situations, it is not possible to identify a distinct source of misinformation, and it appears that the witness may have inferred a false memory by integrating information from a variety of sources. In a stimulus equivalence task, a small number of trained relations between some members of a class of arbitrary stimuli result in a large number of untrained, or emergent relations, between all members of the class.

Attenuation of the disruptive effects of (+/-)3,4-methylenedioxymethamphetamine and cocaine on delayed matching-to-sample performance with D1 versus D2 antagonists.

Evidence suggests that acute exposure to (+/-)3,4-methylenedioxymethamphetamine (MDMA) produces qualitatively similar effects on recognition task performance as other stimulant-type drugs. The current study examined whether there was a similar neurochemical basis to these memory effects by examining the effects of a D1 receptor antagonist (SCH23390) and D2 antagonist (eticlopride) on MDMA- or cocaine-induced impairments in delayed matching-to-sample performance in rats. At low doses it was shown that eticlopride was ineffective in antagonizing either MDMA or cocaine's effects, and at higher doses exacerbated their effects.

Novel object recognition memory: measurement issues and effects of MDMA self-administration following short inter-trial intervals.

The present study was undertaken to examine effects of self-administered MDMA on novel object exploration (NOR) memory. Self-administration was conducted during daily 2 h tests that continued until a total of 165 mg/kg was self-administered (range = 13-41 days for individual rats). Control rats were placed in the self-administration boxes during daily sessions but did not receive any drug.

Anchoring effects in the development of false childhood memories.

When people receive descriptions or doctored photos of events that never happened, they often come to remember those events. But if people receive both a description and a doctored photo, does the order in which they receive the information matter? We asked people to consider a description and a doctored photograph of a childhood hot air balloon ride, and we varied which medium they saw first. People who saw a description first reported more false images and memories than did people who saw a photo first, a result that fits with an anchoring account of false childhood memories.

Human performance on a two-alternative rapid-acquisition choice task.

Davison and Baum [Davison, M., Baum, W. M.

Psychotropic placebos reduce the misinformation effect by increasing monitoring at test.

A psychotropic placebo can help people resist the misinformation effect, an effect thought to be caused by a shift to more stringent source monitoring. When this shift occurs has been unclear. To address this issue we gave some people - but not others - a phoney cognitive-enhancing drug we called R273.

Psychotropic placebos create resistance to the misinformation effect.

Can a placebo for a psychotropic drug help participants resist the misinformation effect? To answer this question, we gave participants a mixture of baking soda and water and told half of them that the mixture was a cognition-enhancing drug called R273 and told the other half that it was an inactive version of the drug. Shortly thereafter, all participants took part in a three-stage misinformation experiment. Compared with participants who were told that they had taken the placebo, the participants who were told that they had taken the drug reported improved cognitive abilities and were less susceptible to the misinformation effect.

The effect of Parkinson's disease on time estimation as a function of stimulus duration range and modality.

The present research sought to investigate the role of the basal ganglia in timing of sub- and supra-second intervals via an examination of the ability of people with Parkinson's disease (PD) to make temporal judgments in two ranges, 100-500 ms, and 1-5 s. Eighteen non-demented medicated patients with PD were compared with 14 matched controls on a duration-bisection task in which participants were required to discriminate auditory and visual signal durations within each time range. Results showed that patients with PD exhibited more variable duration judgments across both signal modality and duration range than controls, although closer analyses confirmed a timing deficit in the longer duration range only.

Attenuation of the disruptive effects of (+/-)3,4-methylene dioxymethamphetamine (MDMA) on delayed matching-to-sample performance in the rat.

Recent evidence suggests that the disruptive effects of acute exposure to (+/-)3,4-methylene dioxymethamphetamine (MDMA) on memory performance may be the result of increased confusion between previous-trial and current-trial events. The current study tested this hypothesis by examining the effects of MDMA on performance of rats in a delayed matching-to-sample procedure when the length of the intertrial interval (ITI) was altered. Consistent with the possibility that limiting the conditions under which responses made on a previous trial would interfere with current-trial choice, a 15-s ITI ameliorated the disruptive effects caused by MDMA on trial performance when the ITI was 5 s.

Dopamine agonists and antagonists can produce an attenuation of response bias in a temporal discrimination task depending on discriminability of target duration.

The current study examined the effects of the D2 agonist (quinpirole) and D2 antagonist (eticlopride) on temporal discrimination performance in a conditional discrimination task (Experiment I) and a delayed conditional discrimination task (Experiment II). In both experiments rats discriminated between a scheduled stimulus duration of 3 s versus 9 s. Consistent with previous reports, overall discrimination performance decreased in a dose-dependent manner with both drugs.

(+/-)3,4-methylenedioxymethamphetamine, d-amphetamine, and cocaine impair delayed matching-to-sample performance by an increase in susceptibility to proactive interference.

This study compared the effects of (+/-)3,4-methylenedioxymethamphetamine, d-amphetamine, and cocaine on performance of rats in a delayed matching-to-sample procedure using a variety of indices of performance to determine the mechanism by which working memory task impairments arise. All 3 drugs produced an overall delay-independent decrease in accuracy rather than a delay-dependent increase in the rate of forgetting. This impairment arose as a result of current-trial choice responses being progressively more affected by responses made in the immediately preceding trial as drug dose increased.

Choice with initial and terminal link reinforcement: an alternative self-control paradigm.

Self-control is demonstrated when a less desirable immediate outcome is chosen to ensure a substantially better future. In a novel animal analogue of this situation, primary reinforcement was delivered in both the initial and terminal links of a concurrent chain schedule. Rats made initial link choices between equal amounts of ethanol-free or ethanol-containing milk.

Self-initiated versus externally cued reaction times in Parkinson's disease.

It has long been observed that patients with Parkinson's disease (PD) can sometimes react and move quickly in response to an external stimulus in a way that they cannot when required to initiate the movement themselves. This curious phenomenon has sometimes been called 'paradoxical kinesis'. The present study was an attempt to demonstrate this phenomenon in patients with PD using an objective and quantifiable experimental procedure.