Faculty Bibliography

The present experiments were undertaken to clarify the role of central alpha(1)-adrenoceptors in reward processes. Rats, trained to self-stimulate via electrodes in the medial forebrain bundle of the lateral hypothalamus, were administered alpha(1)-selective drugs near the locus coeruleus (LC), a site of a dense concentration of alpha(1)-receptors. Effects on reward potency were assessed from shifts in rate-frequency curves while effects on motor response capacity were judged from changes in the maximal rates of responding. It was found that local blockade of LC alpha(1)-receptors with terazosin produced a significant dose-dependent and site-dependent rightward shift of 0.08 log units and a significant decrease of 16.3% in the maximum response rate. Both effects were completely reversed by coadministration of the alpha(1)-agonist, phenylephrine and were not attributable to terazosin's weak action at alpha(2)-adrenoceptors. It is concluded that LC alpha(1)-adrenoceptors are involved both in reward/motivational processes and operant response elaboration which are postulated to work together to facilitate goal attainment.Neuropsychopharmacology advance online publication, 5 July 2006; doi:10.1038/sj.npp.1301145

Effective January 1, 2001, New York State enacted the Expanded Syringe Access Demonstration Program (ESAP), allowing syringes to be sold in pharmacies without a prescription or dispensed through doctors, hospitals, and clinics to adults. A concern in the assessment of ESAP is its effects on syringe disposal practices. Syringe use data regarding the last injection episode were combined from three projects (N = 1,030) recruiting injection drug users. Disposal of syringes by methods known to be safe decreased significantly over time after the implementation of ESAP. Syringes obtained either from syringe exchange programs or ESAP sources were more likely to be disposed of safely than syringes obtained from other sources. Efforts to enlist pharmacists and others involved in ESAP implementation to encourage safe disposal are needed. More detailed information on disposal practices is needed to capture the continuum from least to most safe practices and variation within individuals.

OBJECTIVES: Research has indicated that there is minimal use of pharmacies among injection drug users (IDUs) in specific neighborhoods and among Black and Hispanic IDUs. We developed a community-based participatory research partnership to determine whether a multilevel intervention would increase sterile syringe access through a new policy allowing nonprescription syringe sales in pharmacies. METHODS: We targeted Harlem, NY (using the South Bronx for comparison), and disseminated informational material at community forums, pharmacist training programs, and counseling or outreach programs for IDUs. We compared cross-sectional samples in 3 target populations (pre- and postintervention): community members (attitudes and opinions), pharmacists (opinions and practices), and IDUs (risk behaviors). RESULTS: Among community members (N = 1496) and pharmacists (N = 131), negative opinions of IDU syringe sales decreased in Harlem whereas there was either no change or an increase in negative opinions in the comparison community. Although pharmacy use by IDUs (N=728) increased in both communities, pharmacy use increased significantly among Black IDUs in Harlem, but not in the comparison community; syringe reuse significantly decreased in Harlem, but not in the comparison community. CONCLUSIONS: Targeting the individual and the social environment through a multilevel community-based intervention reduced high-risk behavior, particularly among Black IDUs.

Sexually active non-injection drug users in New York City and their sexual partners or fellow drug users (N = 264) were recruited from 2002 to 2005, and associations between social network characteristics and sexual risk behaviors were examined. We assessed social networks, sexual practices, and drug use. Results suggest having a drug-centered social network, i.e., a network that includes a high proportion of individuals who provide, receive, or use drugs, increases the risk of engaging in high-risk sexual behaviors. The study's limitations are noted and longitudinal studies are needed to ascertain whether these associations are causal. Funding was provided by the National Institute on Drug Abuse.

Inhibition of the acoustic startle response by a smaller preliminary nonstartling stimulus is termed prepulse inhibition (PPI). Schizophrenia patients have impairments in PPI that may not fully normalize even when they are clinically stable on medication, particularly typical antipsychotics. There is evidence that more severe symptoms are associated with more severe PPI abnormalities, but the effect of antipsychotics on this relationship is not clear. Seventy-three male schizophrenia patients underwent acoustic startle and PPI testing. Symptom ratings were performed using the Brief Psychiatric Rating Scale (BPRS) and its subscales. Fifty-two subjects were treated with antipsychotic medication at time of testing; 21 were unmedicated. For all subjects, PPI was negatively correlated with the BPRS psychological discomfort subscale but not with BPRS total symptoms, BPRS positive symptoms or BPRS negative symptoms. For medicated subjects analyzed separately, there were no correlations with BPRS total scores or any subscales. For the unmedicated subjects analyzed separately, there were significant correlations of lower PPI with greater severity of BPRS total symptoms, positive symptoms and the psychological discomfort subscale. These data indicate that more severe symptoms are associated with lower PPI, but that medication status is an important factor in the relationship between symptom severity and sensorimotor gating

Chronic food restriction (FR) enhances the rewarding and motor-activating effects of abused drugs, and is accompanied by changes in dopamine (DA) dynamics and increased D-1 DA receptor-mediated cell signaling and transcriptional responses in nucleus accumbens (NAc). However, little is known about effects of FR on DA synthetic activity in the mesoaccumbens and nigrostriatal pathways. In Experiment 1 of the present study, tyrosine hydroxylase (TH) gene expression was measured in ventral tegmental area and substantia nigra, using real-time RT-PCR and in situ hybridization; no differences were observed between FR and ad libitum fed (AL) rats. In Experiment 2, TH protein levels, determined by Western blot, were found to be elevated in NAc and caudate-putamen (CPu) of FR relative to AL rats. In the absence of increased transcription, this may reflect a slowing of TH degradation. In Experiments 3 and 4, DA synthetic activity was assessed by Western blot measurement of TH phosphorylation at Ser40, and HPLC measurement of in vivo tyrosine hydroxylation rate, as reflected by DOPA accumulation following administration of a decarboxylase inhibitor (NSD-1015; 100 mg/kg, i.p.). Basal phospho-(Ser40)-TH levels did not differ between groups but DOPA accumulation was decreased by FR. Decreased DOPA synthesis, despite increased levels of TH protein, may reflect the inhibitory effect of increased DA binding to TH protein or decreased concentrations of cofactor tetrahydrobiopterin. Finally, in response to D-amphetamine (0.5 and 5.0 mg/kg, i.p.), phospho-(Ser40)-TH was selectively decreased in NAc of FR rats. This suggests increased feedback inhibition of DA synthesis-a possible consequence of postsynaptic receptor hypersensitivity, or increased extracellular DA concentration. These results indicate that FR increases TH protein levels, but may decrease the capacity for DA synthesis by decreasing TH activity. According to this scheme, the previously observed upregulation of striatal cell signaling and transcriptional responses to DA receptor agonist administration may include compensatory neuroadaptations

We compared sexual behaviors/partnerships and determined sexual risk correlates associated with HIV by gender among street-recruited drug users using chi-square tests and logistic regression. Men reported higher risk sexual behaviors, yet fewer high-risk sexual partners than women. After adjustment, HIV seropositive men were more likely than seronegatives to be older, MSM, use condoms, and have an HIV-infected partner. HIV seropositive women were more likely to be older, have an HIV-infected partner, and not use non-injected heroin. IDU was not associated with HIV. Prospective studies are needed to determine how gender-specific sexual behaviors/partnerships among drug users affect HIV acquisition.