Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons

In the present study, we analyzed mice with a targeted deletion of β-catenin in DA neurons (DA-βcat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-βcat KO mice showed significant deficits in their ability to form long-term memories and displayed reduced expression of methamphetamine-induced behavioral sensitization after subsequent challenge doses with this drug, suggesting that motor learning and drug-induced learning plasticity are altered in these mice. Morphological analyses showed no changes in the number or distribution of tyrosine hydroxylase-labeled neurons in the ventral midbrain. While electrochemical measurements in the striatum determined no changes in acute DA release and uptake, a small but significant decrease in DA release was detected in mutant animals after prolonged repetitive stimulation, suggesting a possible deficit in the DA neurotransmitter vesicle reserve pool. However, electron microscopy analyses did not reveal significant differences in the content of synaptic vesicles per terminal, and striatal DA levels were unchanged in DA-βcat KO animals. In contrast, striatal mRNA levels for several markers known to regulate synaptic plasticity and DA neurotransmission were altered in DA-βcat KO mice. This study demonstrates that ablation of β-catenin in DA neurons leads to alterations of motor and reward-associated memories and to adaptations of the DA neurotransmitter system and suggests that β-catenin signaling in DA neurons is required to facilitate the synaptic remodeling underlying the consolidation of long-term memories.     

Neighborhood social disorder as a determinant of drug injection behaviors: a structural equation modeling approach.

Neighborhood environments are increasingly recognized as a contextual determinant of health, behaviors, and disease; however, the pathways through which neighborhood characteristics impact health behaviors are poorly understood. This article examines pathways to elucidate how neighborhood social disorder may lead to HIV transmission. Data are from a baseline survey of 701 injection drug users from the Self-Help in Eliminating Lethal Diseases Study, an HIV prevention intervention in Baltimore. Structural equation modeling was used to examine the pathways among social disorder, psychological distress, and drug injection behaviors. The relationship between disorder and injection behaviors in the models tested suggests that psychological distress is higher in more socially disordered neighborhoods, that distress leads to greater injection frequency and equipment sharing, and that injection frequency predicts equipment sharing.     

Social Integration and Suicide‐Related Ideation from a Social Network Perspective: A Longitudinal Study among Inner‐City African Americans

Social network density, as measured by the extent to which network members know each other, was examined to determine whether it is associated with suicide‐related ideation and plan approximately 3 years later. Eight hundred and nineteen African Americans were interviewed at Wave 1 (1997–1999) and Wave 4 (2001–2003) of the Self‐Help In Eliminating Life‐Threatening Diseases (SHIELD) study, a HIV preventive intervention study in Baltimore, MD. Multinomial logistic regression models were used to compare risks of suicide‐related ideation and plan at Wave 4 by Wave 1 density. Even after adjusting for baseline sociodemographic characteristics and depressive symptoms, individuals with a lower level of density were three times more likely to report suicide‐related ideation and plan in the past year at Wave 4. The findings reinforce the importance of social integration among inner‐city African Americans from a social network perspective. Future research should examine the mechanisms associated with this relationship and other social network constructs.