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.

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.

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.

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.

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.

Modulation of spinal glial reactivity by intrathecal PPF is not sufficient to inhibit mechanical allodynia induced by nerve crush.

Spinal glial reactivity has been strongly implicated in pain that follows peripheral nerve injury. Among the many therapeutic agents that have been tested for anti-allodynia through immune modulation is the atypical methylxanthine propentofylline. While propentofylline shows a potent anti-allodynia effect after nerve transection injury, we here demonstrate that, when propentofylline is used intrathecally at the effective immune-modulatory dose, allodynia after rat nerve crush injury is completely preserved.