Dissociable Roles of the mPFC-to-VTA Pathway in the Control of Impulsive Action and Risk-Related Decision-Making in Roman High- and Low-Avoidance Rats.

Background: Impulsive action and risk-related decision-making (RDM) are associated with various psychiatric disorders, including drug abuse. Both behavioral traits have also been linked to reduced frontocortical activity and alterations in dopamine function in the ventral tegmental area (VTA). However, despite direct projections from the medial prefrontal cortex (mPFC) to the VTA, the specific role of the mPFC-to-VTA pathway in controlling impulsive action and RDM remains unexplored.

Decoupling Dopamine Synthesis from Impulsive Action, Risk-Related Decision-Making, and Propensity to Cocaine Intake: A Longitudinal [F]-FDOPA PET Study in Roman High- and Low-Avoidance Rats.

Impulsive action and risk-related decision-making (RDM) are two facets of impulsivity linked to a hyperdopaminergic release in the striatum and an increased propensity to cocaine intake. We previously showed that with repeated cocaine exposure, this initial hyperdopaminergic release is blunted in impulsive animals, potentially signaling drug-induced tolerance. Whether such dopaminergic dynamics involve changes in dopamine (DA) synthesis as a function of impulsivity is currently unknown.

Repeated Cocaine Intake Differentially Impacts Striatal D Receptor Availability, Psychostimulant-Induced Dopamine Release, and Trait Behavioral Markers of Drug Abuse.

Current research indicates that altered dopamine (DA) transmission in the striatum contributes to impulsivity and novelty-seeking, and it may mediate a link concerning a higher susceptibility to drug abuse. Whether increased susceptibility to drug abuse results from a hyperdopaminergic or hypodopaminergic state is still debated. Here, we simultaneously tracked changes in DA D receptor (DR) availability and amphetamine-(AMPH)-induced DA release in relation to impulsivity and novelty-seeking prior to, and following, cocaine self-administration (SA) in Roman high- (RHA) and low- (RLA) avoidance rats.

Motor impulsivity but not risk-related impulsive choice is associated to drug intake and drug-primed relapse.

Introduction: Motor impulsivity and risk-related impulsive choice have been proposed as vulnerability factors for drug abuse, due to their high prevalence in drug abusers. However, how these two facets of impulsivity are associated to drug abuse remains unclear. Here, we investigated the predictive value of both motor impulsivity and risk-related impulsive choice on characteristics of drug abuse including initiation and maintenance of drug use, motivation for the drug, extinction of drug-seeking behavior following drug discontinuation and, finally, propensity to relapse.

A cycle-consistent adversarial network for brain PET partial volume correction without prior anatomical information.

Purpose: Partial volume effect (PVE) is a consequence of the limited spatial resolution of PET scanners. PVE can cause the intensity values of a particular voxel to be underestimated or overestimated due to the effect of surrounding tracer uptake. We propose a novel partial volume correction (PVC) technique to overcome the adverse effects of PVE on PET images.

Concurrent measures of impulsive action and choice are partially related and differentially modulated by dopamine D- and D-like receptors in a rat model of impulsivity.

Impulsivity is a multidimensional construct, but the relationships between its constructs and their respective underlying dopaminergic underpinnings in the general population remain unclear. A cohort of Roman high- (RHA) and low- (RLA) avoidance rats were tested for impulsive action and risky decision-making in the rat gambling task, and then for delay discounting in the delay-discounting task to concurrently measure the relationships among the three constructs of impulsivity using a within-subject design. Then, we evaluated the effects of dopaminergic drugs on the three constructs of impulsivity, considering innate differences in impulsive behaviors at baseline.

Electrophysiological and behavioral correlates of cannabis use disorder.

Current research indicates deficits in cognitive function together with widespread changes in brain activity following long-term cannabis use. In particular, cannabis use has been associated with excessive spectral power of the alpha rhythm (8-12 Hz), which is also known to be modulated during attentional states. Recent neuroimaging studies have linked heavy cannabis use with structural and metabolic changes in the brain; however, the functional consequences of these changes are still not fully characterized.

Early environmental enrichment and impoverishment differentially affect addiction-related behavioral traits, cocaine-taking, and dopamine D receptor signaling in a rat model of vulnerability to drug abuse.

Rationale: Risk factors for drug addiction include genetics, environment, and behavioral traits such as impulsivity and novelty preference (NP), which have been related to deficits in striatal dopamine (DA) D-receptors (DR) and heightened amphetamine (AMPH)-induced DA release. However, the influence of the early rearing environment on these behavioral and neurochemical variables is not clear.

Objectives: We investigated the influence of early rearing environment on striatal DR availabilities and AMPH-induced DA release in relation to impulsivity, NP, and propensity to drug self-administration (SA) in "addiction-prone" Roman high- (RHA) and "addiction-resistant" Roman low-avoidance (RLA) rats.

Fast dynamic brain PET imaging using stochastic variational prediction for recurrent frame generation.

Purpose: We assess the performance of a recurrent frame generation algorithm for prediction of late frames from initial frames in dynamic brain PET imaging.

Methods: Clinical dynamic F-DOPA brain PET/CT studies of 46 subjects with ten folds cross-validation were retrospectively employed. A novel stochastic adversarial video prediction model was implemented to predict the last 13 frames (25-90 minutes) from the initial 13 frames (0-25 minutes).

PET Imaging of Dopamine Neurotransmission During EEG Neurofeedback.

Neurofeedback (NFB) is a brain-based training method that enables users to control their own cortical oscillations using real-time feedback from the electroencephalogram (EEG). Importantly, no investigations to date have directly explored the potential impact of NFB on the brain's key neuromodulatory systems. Our study's objective was to assess the capacity of NFB to induce dopamine release as revealed by positron emission tomography (PET).

Effect of 5-HT2A receptor antagonism on levels of D2/3 receptor occupancy and adverse behavioral side-effects induced by haloperidol: a SPECT imaging study in the rat.

Several studies suggested that 5-HT receptor (5-HTR) blockade may provide a more favorable efficacy and side-effect profile to antipsychotic treatment. We hypothesized that a combined haloperidol (a D receptor (DR) antagonist) and MDL-100,907 (a 5-HTR antagonist) treatment would reverse the side effects and the neurochemical alterations induced by haloperidol alone and would potentialize its efficacy. We thus chronically treated male Mdr1a knock-out rats with several doses of haloperidol alone or in combination with a saturating dose of a MDL-100,907.

Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats.

Background: Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated.

Methods: We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals.

Deep learning-guided joint attenuation and scatter correction in multitracer neuroimaging studies.

PET attenuation correction (AC) on systems lacking CT/transmission scanning, such as dedicated brain PET scanners and hybrid PET/MRI, is challenging. Direct AC in image-space, wherein PET images corrected for attenuation and scatter are synthesized from nonattenuation corrected PET (PET-nonAC) images in an end-to-end fashion using deep learning approaches (DLAC) is evaluated for various radiotracers used in molecular neuroimaging studies. One hundred eighty brain PET scans acquired using F-FDG, F-DOPA, F-Flortaucipir (targeting tau pathology), and F-Flutemetamol (targeting amyloid pathology) radiotracers (40 + 5, training/validation + external test, subjects for each radiotracer) were included.

Differential involvement of D2 and D3 receptors during reinstatement of cocaine-seeking behavior in the Roman high- and low-avoidance rats.

Roman high- (RHA) and low-avoidance (RLA) rats have been used as a model for drug-addiction, showing, respectively, high- and low-responding to psychostimulants, and low versus high dopamine D2/3 receptors (D2/3R) striatal density. Previous studies indicated a major involvement of D2/3R on reinstatement of cocaine seeking, although the respective role of the two receptor subtypes is not clear. Here, we investigated sensitivity to cocaine self-administration (SA) through a dose-response protocol in RHAs and RLAs, and reinstatement of drug-seeking behavior at 15 days and 5 weeks following withdrawal.

Dynamic image denoising for voxel-wise quantification with Statistical Parametric Mapping in molecular neuroimaging.

Purpose: PET and SPECT voxel kinetics are highly noised. To our knowledge, no study has determined the effect of denoising on the ability to detect differences in binding at the voxel level using Statistical Parametric Mapping (SPM).

Methods: In the present study, groups of subject-images with a 10%- and 20%- difference in binding of [123I]iomazenil (IMZ) were simulated.

Dual-radiotracer translational SPECT neuroimaging. Comparison of three methods for the simultaneous brain imaging of D and 5-HT receptors.

Purpose: SPECT imaging with two radiotracers at the same time is feasible if two different radioisotopes are employed, given their distinct energy emission spectra. In the case of I and I, dual SPECT imaging is not straightforward: I emits photons at a principal energy emission spectrum of 143.1-179.

Different effects of chronic THC on the neuroadaptive response of dopamine D2/3 receptor-mediated signaling in roman high- and roman low-avoidance rats.

The Roman high (RHA)- and low (RLA)-avoidance rat sublines have been identified as an addiction-prone and addiction-resistant phenotype based on their high vs. low locomotor responsiveness to novelty and high vs. low ability to develop neurochemical and behavioral sensitization to psychostimulants, respectively.

A single-scan protocol for absolute D receptor quantification with [I]IBZM SPECT.

Purpose: Molecular imaging of the D receptor is widely used in neuropsychiatric research. Non-displaceable binding potential (BP) is a very popular quantitative index, defined as the product of the receptor concentration (B) and the radiotracer affinity for the receptor (1/appK). As the appK is influenced by parameters such as the endogenous neurotransmitter dynamics, it often constitutes a confounding factor in research studies.

Time-dependent effects of repeated THC treatment on dopamine D2/3 receptor-mediated signalling in midbrain and striatum.

This study examined the time-course of alterations in levels and functional sensitivities of dopamine D2/3 receptors (D2/3R) during the course and up to 6 weeks following cessation of chronic treatment with Delta(9)-Tetrahydrocannabinol (THC) in rats. THC treatment led to an increase in D2/3R levels in striatum, as assessed using [(3)H]-(+)-PHNO, that was readily observable after one week of treatment, remained stably elevated during the subsequent 2 weeks of treatment, but fully reversed within 2 weeks of THC discontinuation. THC-induced D2/3R alterations were more pronounced and longer lasting in the dopamine cell body regions of the midbrain, wherein [(3)H]-(+)-PHNO binding was still elevated at 2 weeks but back to control values at 6 weeks after THC cessation.

5-HT2A receptor SPECT imaging with [¹²³I]R91150 under P-gp inhibition with tariquidar: More is better?

Introduction: Pharmacological P-glycoprotein (P-gp) inhibition with tariquidar (TQD) is considered a promising strategy for the augmentation of radiotracer brain uptake. However, a region-dependent effect may compromise the robustness of quantitative studies. For this reason, we studied the effect of a TQD pretreatment on 5-HT2A imaging with [(123)I]R91150 and compared results with those obtained in Mdr1a knock-out (KO) rats.

In Vivo Quantification of 5-HT2A Brain Receptors in Mdr1a KO Rats with 123I-R91150 Single-Photon Emission Computed Tomography.

Our goal was to identify suitable image quantification methods to image 5-hydroxytryptamine2A (5-HT2A) receptors in vivo in Mdr1a knockout (KO) rats (i.e., P-glycoprotein KO) using 123I-R91150 single-photon emission computed tomography (SPECT).

A modified simplified reference tissue model for the quantification of dopamine D2/3 receptors with [18F]fallypride images.

Defluorination of [18F]fallypride and accumulation of 18F in skull and glands leads to the contamination of brain structures with spillover activity due to partial volume effects, leading to considerable errors in binding potential estimations. Here we propose a modification of the simplified reference tissue model (SRTM) to take into account the contribution of skull activity to the radioactivity kinetic pattern in cerebellum and target regions. It consists of the introduction of an additional parameter for each volume of interest (sT) and one for the cerebellum (sR), corresponding to the fraction of skull activity contaminating these structures.

Repeated but not acute treatment with ∆⁹-tetrahydrocannabinol disrupts prepulse inhibition of the acoustic startle: reversal by the dopamine D₂/₃ receptor antagonist haloperidol.

Cannabis produces cognitive dysfunctions that resemble those of schizophrenia; yet the neurobiological substrate of this similarity remains unclear. Schizophrenia patients show deficits in prepulse inhibition (PPI) of the acoustic startle reflex (ASR), an operational measure of the information-processing abnormalities that may underlie the cognitive and positive symptoms of the disease. However, the effect of cannabis on PPI remains poorly understood, as data are often contradictory.

Small-animal single-photon emission computed tomographic imaging of the brain serotoninergic systems in wild-type and mdr1a knockout rats.

The pharmacokinetic properties of radiotracers are crucial for successful in vivo single-photon emission computed tomographic (SPECT) imaging. Our goal was to determine if MDR1A-deficient animals could allow better SPECT imaging outcomes than wild-type (WT) animals for a selection of serotoninergic radioligands. Thus, we compared the performances of 123I-p-MPPI, 123I-R91150, 123I-SB207710, and 123I-ADAM radioligands, for imaging of their respective targets (5-hydroxytryptamine [5-HT]1A, 5-HT2A, 5-HT4, and serotonin transporter [SERT]), in WT and Mdr1a knockout (KO) rats.