Psychological Impacts of Retained Bullets From the Perspective of Survivors.

INTRODUCTION: Despite a high prevalence of retained bullet fragments (RBFs) after firearm related injury (FRI) there is limited data on the full spectrum of their consequences, particularly the psychological impacts on those injured. Further, the experiences of FRI survivors with RBFs are missing from existing literature. The objective of this study was to explore the psychological impacts of RBFs on individuals who have experienced recent FRI. METHODS: Adult (18-65 years) survivors of FRI with radiographically confirmed RBFs were purposively selected from an urban Level 1 trauma center in Atlanta, Georgia, to participate in an in-depth interview. Interviews were conducted between March 2019 and February 2020. Thematic analysis was used to identify a range of psychological effects from RBFs. RESULTS: Interviews from 24 FRI survivors were analyzed: the majority of participants were Black males (N = 22, 92%) with a mean age of 32 years whose FRI occurred ∼8.6 months prior to data collection. The psychological effects of RBFs were grouped into four categories: physical health (eg, pain, limited mobility), emotional well-being (eg, anger, fear), social isolation, and occupational welfare (eg, disability leading to inability to work). A range of coping mechanisms were also identified. CONCLUSION: Survivors of FRI with RBFs experience a range of psychological impacts that are far-reaching and affect daily activities, mobility, pain and emotional wellbeing. Study results indicate a need for enhanced resources to support those with RBFs. Further, changes to clinical protocols are warranted on removal of RBFs and communication about the effects of leaving RBFs in situ.

Cholecystokinin modulates both the development and the expression of behavioral sensitization to amphetamine in the rat.

RATIONALE: Repeated administration of psychostimulants such as amphetamine (AMPH) produces an enduring augmentation of their locomotor effects. Previous research suggests that this phenomenon, termed sensitization, is related to changes within the mesolimbic dopamine (DA) system. OBJECTIVES: The present experiments were designed to investigate the contribution of endogenous cholecystokinin (CCK), a neuropeptide co-localized with DA in the mesolimbic system, to the development (experiment 1) and the expression (experiment 2) of locomotor sensitization to AMPH. METHODS: In experiment 1, rats were injected (IP) with the CCK(A) antagonist devazepide (0, 0.001, 0.01, or 0.1 mg/kg) or the CCK(B) antagonist L-365,260 (0, 0.001, 0.01, 0.1, or 1.0 mg/kg) followed by AMPH (1.5 mg/kg) once daily for seven days. Following 10 days withdrawal, rats were administered AMPH (0.75 mg/kg) and their locomotor activity recorded. In experiment 2, rats were administered AMPH (1.5 mg/kg) once daily for 7 days. Following 10 days withdrawal, rats were injected with devazepide (0, 0.0001, 0.001, 0.01, 0.1, or 1.0 mg/kg) or L-365,260 (0, 0.001, 0.01, or 0.1 mg/kg) followed 30 min later by AMPH (0.75 mg/kg) and their locomotor activity recorded. RESULTS: When administered during the AMPH pretreatment phase of experiment 1, the two highest doses of L-365,260 attenuated, and the lowest dose of L-365,260 potentiated, the sensitized locomotor response to AMPH challenge. When administered prior to the AMPH challenge phase of experiment 2, devazepide attenuated the sensitized locomotor response to AMPH. CONCLUSIONS: These results suggest that CCK(B) and CCK(A) receptors modulate the development and the expression of behavioral sensitization to AMPH, respectively.

Self-administration of intravenous amphetamine is predicted by individual differences in sucrose feeding in rats.

RATIONALE: Previous studies have shown that individual differences in oral sucrose consumption are predictive of the psychomotor and dopamine (DA) stimulant properties of amphetamine in rats. OBJECTIVES: The present experiment was designed to examine the relationship between sucrose feeding and the reinforcing properties of amphetamine using the intravenous (i.v.) drug self-administration paradigm. METHODS: Based on a median split of sucrose intake during a final 1-h feeding test session, male Wistar rats were designated as either low (LSF) or high sucrose feeders (HSF). Acquisition of i. v.-amphetamine self-administration across ten daily 30-min sessions was then assessed. Following acquisition, i.v. self-administration of several doses of amphetamine was similarly tested across daily 30-min sessions. RESULTS: Data from this experiment revealed augmented responding in HSF compared with LSF during acquisition of amphetamine self-administration. Correspondingly, when given access to different doses of amphetamine, responding was greater in HSF than in LSF across several doses (3 microg and 10 microg per infusion). CONCLUSIONS: These data support the notion that individual differences in oral sucrose consumption are predictive of the reinforcing properties of psychostimulant drugs.

Self-administration of intravenous amphetamine: effect of nucleus accumbens CCKB receptor activation on fixed-ratio responding.

RATIONALE: The mesolimbic dopamine (DA) system is implicated in psychostimulant drug self-administration. The neuropeptide cholecystokinin (CCK) is co-localised with DA and inhibits nucleus accumbens (NAcc) DAergic neurotransmission via CCKB receptors. OBJECTIVES: The present experiment was designed to examine the effects of intra-NAcc CCKB receptor stimulation on fixed-ratio (FR) amphetamine self-administration. METHODS: Wistar rats with intravenous catheters and NAcc cannulae were trained to self-administer amphetamine under a FR3 schedule of reinforcement. Animals performing stable self-administration were microinjected with pentagastrin and assessed during 3-h sessions. RESULTS: Intra-NAcc pentagastrin dose dependently increased amphetamine intake. CONCLUSIONS: These results are consistent with the notion that NAcc CCKB receptor activation attenuates amphetamine reward.

Stimulation of GABAB receptors in the basal forebrain selectively impairs working memory of rats in the double Y-maze.

The present experiments were conducted to evaluate the possible contribution of GABAergic inputs to the basal forebrain in the region of the nucleus basalis magnocellularis (nbm) to memory. In two experiments, rats implanted with bilateral intra-nbm guide cannulae were trained in the double Y-maze task to perform working- and reference-memory components. Animals were placed in one of two start arms of the first "Y" and the reference-memory component required travelling to its central stem for food. Access to the second "Y" then was given and the working-memory component for Expt. 1 required travelling to the goal arm diagonally opposite the start arm in the first "Y" of that trial. In Expt. 2, the working-memory component required travelling to the goal arm opposite to the goal arm entered in the second "Y" on the preceding trial, with 0- and 15-s delays between trials. In Expt. 1, pretrained rats (n = 8) received the GABAA agonist, muscimol (0.1 microgram in 0.5 microliter), the GABAB agonist, R(+)-baclofen (0.01, 0.05 and 0.1 microgram), and its less active enantiomer, S(-)-baclofen (0.1 microgram), in a counterbalanced order with retraining to criterion between injections. In Expt. 2, pretrained rats (n = 9) received saline (0.5 microliter), R(+)-baclofen (0.1 microgram), the GABAB antagonist, phaclofen (1 microgram), and R(+)-baclofen+phaclofen. Results of Expt. 1 revealed that intra-nbm muscimol and, in a dose-dependent manner, R(+)-baclofen differentially affected working but not reference memory. In Expt. 2, the differential mnemonic impairment produced by R(+)-baclofen was replicated and co-injection with phaclofen reversed this effect. A 15-s delay between trials significantly impaired working but not reference memory. Results suggest that both GABAA and GABAB receptors may be involved in modulating the possible mnemonic functions of nbm cholinergic neurons.

Injections of D-amphetamine into the ventral pallidum increase locomotor activity and responding for conditioned reward: a comparison with injections into the nucleus accumbens.

The nucleus accumbens and ventral pallidum receive dopamine (DA) projections from the mesencephalon. Although DA inputs to the nucleus accumbens are implicated in both locomotion and reward processes, little is known of the behavioural significance of DA in the ventral pallidum. These studies examined the effects of D-amphetamine injected into the nucleus accumbens or ventral pallidum on locomotor activity and responding for a conditioned reward (CR). In the nucleus accumbens D-amphetamine dose dependently (1, 3 and 10 microg) increased locomotion within 5-10 min of injection. Intra-ventral pallidum microinjections of D-amphetamine also increased activity in this dose range, but the effect occurred with a longer latency (5-20 min). The magnitude of the response evoked by ventral pallidum injections was lower than that evoked by nucleus accumbens injections. The GABAA antagonist picrotoxin (0.1 microg) stimulated activity when injected into the ventral pallidum but not the nucleus accumbens, providing a pharmacological dissociation between the two injection sites. In the CR studies, D-amphetamine injected into both sites potentiated responding for a CR previously paired with food delivery, without altering responding on an inactive lever. Picrotoxin injected into the ventral pallidum reduced responding and abolished the selectivity of responding for CR. The results show that DA release in the ventral pallidum enhances locomotion and responding for a CR, providing evidence that DA in the ventral pallidum plays a significant role in the mediation of the effects of D-amphetamine. The failure of picrotoxin to elevate responding for CR despite increasing locomotor activity indicates that pharmacologically-induced blockade of GABAA receptors in the ventral pallidum disrupts goal-directed responding.

The expression of behavioral sensitization to amphetamine: role of CCK(A) receptors.

These studies investigated whether endogenous activation of CCK(A) receptors mediates the expression of amphetamine (AMP)-induced locomotor activity. In Experiment 1, locomotor activity was assessed in rats pretreated with the CCK(A) antagonist devazepide (0.001, 0.01, and 0.1 mg/kg) and subsequently injected with AMP (1.5 mg/kg). In Experiment 2, rats were administered AMP (1.5 mg/kg) once daily for 7 days. Following a 10-day withdrawal, locomotor activity was assessed following treatment with devazepide (0.001, 0.01, and 0.1 mg/kg) and AMP (0.75 mg/kg). In both studies, rats were classified as low (LR) or high (HR) responders based upon a median split of their locomotor response to a novel environment. Results from Experiment 1 showed that AMP potentiated the expression of locomotor activity, and this effect was most pronounced in HR rats. However, devazepide did not affect AMP-induced locomotion. Results from Experiment 2 demonstrated that chronic AMP pretreatment augmented the locomotor response to subsequent AMP challenge, and this effect was most pronounced in the HR group. Further, this augmented response was blocked by devazepide in HR rats. These findings constitute the first demonstration that endogenous CCK(A) receptor activation is an important substrate mediating AMP-induced locomotor activity in animals with a previous history of AMP treatment.

Individual differences in sucrose intake predict behavioral reactivity in rodent models of anxiety.

We have previously shown that individual differences in oral sucrose consumption are predictive of behavioral reactivity of rats in the elevated plus-maze (EPM). The present experiments were designed to replicate the EPM results and to extend them to another animal model of anxiety, the acoustic startle reflex (ASR) paradigm. In two experiments, sucrose consumption was assessed in separate groups of rats across eight daily 1-h feeding sessions. Animals were designated as either low (LSF) or high sucrose feeders (HSF) based on a median split of their sucrose intake on the final test day. Following this assay, animals were tested in the EPM in Experiment 1, and in the ASR paradigm in Experiment 2. Results from Experiment 1 replicated our previous findings and showed that the percentage of time spent on, and entries into, open arms was significantly lower in LSF than HSF. Further, results from Experiment 2 revealed a significantly augmented startle response to acoustic stimuli (94-108 dB SPL) in LSF compared to HSF. These data provide converging evidence to support the notion that individual differences in baseline levels of oral sucrose consumption are predictive of anxious behaviors in rats.

Use of an on-line pager system to increase adherence to antiretroviral medications.

Adherence to antiretroviral therapy is critical for treatment success. Antiretroviral therapy typically requires multiple pills at multiple dosing times. To address this, we tested the feasibility, utility, and efficacy of a customizable reminder system using pagers, which were programmed using web-based technology, to increase and maintain proper adherence in patients with pre-existing adherence problems. After a two-week monitoring period with an electronic pill-cap, participants with less than 90% adherence were randomized to continue monitoring or to receive a pager. The group who received the pagers had greater improvements in adherence from baseline to Week 2 and Week 12 than those who monitored their medications only. However, adherence in both groups at the outcome assessments points was still poor. While the provision of a reminder system helped improve adherence, it is likely that more intensive interventions are required for patients with pre-existing problems.