Faculty and Staff

Illicit psychostimulant addiction remains a significant problem worldwide, despite decades of research into the neural underpinnings and various treatment approaches. The purpose of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in humans. Investigational pharmacological treatments for illicit psychostimulant addiction are also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs.

Attention deficit/hyperactivity disorder (ADHD) is a risk factor for tobacco use and dependence. This study examines the responsiveness to nicotine of an adolescent model of ADHD, the spontaneously hypertensive rat (SHR). The conditioned place preference (CPP) procedure was used to assess nicotine-induced locomotion and conditioned reward in SHR and the Wistar Kyoto (WKY) control strain over a range of nicotine doses (0.0, 0.1, 0.3 and 0.6 mg/kg). Prior to conditioning, SHRs were more active and less biased toward one side of the CPP chamber than WKY rats. Following conditioning, SHRs developed CPP to the highest dose of nicotine (0.6 mg/kg), whereas WKYs did not develop CPP to any nicotine dose tested. During conditioning, SHRs displayed greater locomotor activity in the nicotine-paired compartment than in the saline-paired compartment across conditioning trials. SHRs that received nicotine (0.1, 0.3, 0.6 mg/kg) in the nicotine-paired compartment showed an increase in locomotor activity between conditioning trials. Nicotine did not significantly affect WKY locomotor activity. These findings suggest that the SHR strain is a suitable model for studying ADHD-related nicotine use and dependence, but highlights potential limitations of the WKY control strain and the CPP procedure for modeling ADHD-related nicotine reward.

Positive allosteric modulators (PAMs) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a diverse class of compounds that increase fast excitatory transmission in the brain. AMPA PAMs have been shown to facilitate long-term potentiation, strengthen communication between various cortical and subcortical regions, and some of these compounds increase the production and release of brain-derived neurotrophic factor (BDNF) in an activity-dependent manner. Through these mechanisms, AMPA PAMs have shown promise as broad spectrum pharmacotherapeutics in preclinical and clinical studies for various neurodegenerative and psychiatric disorders. In recent years, a small collection of preclinical animal studies has also shown that AMPA PAMs may have potential as pharmacotherapeutic adjuncts to extinction-based or cue-exposure therapies for the treatment of drug addiction. The present paper will review this preclinical literature, discuss novel data collected in our laboratory, and recommend future research directions for the possible development of AMPA PAMs as anti-addiction medications.

Background: Foam rolling has been shown to acutely increase range of motion (ROM) during knee flexion and hip flexion with the experimenter applying an external force, yet no study to date has measured hip extensibility as a result of foam rolling with controlled knee flexion and hip extension moments. The purpose of this study was to investigate the acute effects of foam rolling on hip extension, knee flexion, and rectus femoris length during the modified Thomas test.

Methods: Twenty-three healthy participants (male = 7; female = 16; age = 22 ± 3.3 years; height = 170 ± 9.18 cm; mass = 67.7 ± 14.9 kg) performed two, one-minute bouts of foam rolling applied to the anterior thigh. Hip extension and knee flexion were measured via motion capture before and after the foam rolling intervention, from which rectus femoris length was calculated.

Results: Although the increase in hip extension (change = +1.86° (+0.11, +3.61); z(22) = 2.08; p = 0.0372; Pearson’s r = 0.43 (0.02, 0.72)) was not due to chance alone, it cannot be said that the observed changes in knee flexion (change = −1.39° (−5.53, +2.75); t(22) = −0.70; p = 0.4933; Cohen’s d = − 0.15 (−0.58, 0.29)) or rectus femoris length (change = −0.005 (−0.013, +0.003); t(22) = −1.30; p = 0.2070; Cohen’s d = − 0.27 (−0.70, 0.16)) were not due to chance alone.

Conclusions: Although a small change in hip extension was observed, no changes in knee flexion or rectus femoris length were observed. From these data, it appears unlikely that foam rolling applied to the anterior thigh will improve passive hip extension and knee flexion ROM, especially if performed in combination with a dynamic stretching protocol.

Muscle hypertrophy and atrophy occur frequently as a result of mechanical loading or unloading, with implications for clinical, general, and athletic populations. The effects of muscle hypertrophy and atrophy on force production and joint moments have been previously described. However, there is a paucity of research showing how hypertrophy and atrophy may affect moment arm (MA) lengths. The purpose of this model was to describe the mathematical relationship between the anatomical cross-sectional area (ACSA) of a muscle and its MA length. In the model, the ACSAs of the biceps brachii and brachialis were altered to hypertrophy up to twice their original size and to atrophy to one-half of their original size. The change in MA length was found to be proportional to the arcsine of the square root of the change in ACSA. This change in MA length may be a small but important contributor to strength, especially in sports that require large joint moments at slow joint angular velocities, such as powerlifting. The paradoxical implications of the increase in MA are discussed, as physiological factors influencing muscle contraction velocity appear to favor a smaller MA length for high velocity movements but a larger muscle MA length for low velocity, high force movements.

Background: The purpose of this study was to compare the peak electromyography (EMG) of the most commonly-used position in the literature, the prone bent-leg (90°) hip extension against manual resistance applied to the distal thigh (PRONE), to a novel position, the standing glute squeeze (SQUEEZE).

Methods: Surface EMG electrodes were placed on the upper and lower gluteus maximus of thirteen recreationally active females (age = 28.9 years; height = 164 cm; body mass = 58.2 kg), before three maximum voluntary isometric contraction (MVIC) trials for each position were obtained in a randomized, counterbalanced fashion.

Results: No statistically significant (p < 0.05) differences were observed between PRONE (upper: 91.94%; lower: 94.52%) and SQUEEZE (upper: 92.04%; lower: 85.12%) for both the upper and lower gluteus maximus. Neither the PRONE nor SQUEEZE was more effective between all subjects.

Conclusions: In agreement with other studies, no single testing position is ideal for every participant. Therefore, it is recommended that investigators employ multiple MVIC positions, when possible, to ensure accuracy. Future research should investigate a variety of gluteus maximus MVIC positions in heterogeneous samples.

Many strength and conditioning coaches utilize the good morning (GM) to strengthen the hamstrings and spinal erectors. However, little research exists on its electromyography (EMG) activity and kinematics, and how these variables change as a function of load. The purpose of this investigation was to examine how estimated hamstring length, integrated EMG (IEMG) activity of the hamstrings and spinal erectors, and kinematics of the lumbar spine, hip, knee, and ankle are affected by changes in load. Fifteen trained male participants (age = 24.6 ± 5.3 years; body mass = 84.7 ± 11.3 kg; height = 180.9 ± 6.8 cm) were recruited for this study. Participants performed five sets of the GM, utilizing 50, 60, 70, 80, and 90% of one-repetition maximum (1RM) in a randomized fashion. IEMG activity of hamstrings and spinal erectors tended to increase with load. Knee flexion increased with load on all trials. Estimated hamstring length decreased with load. However, lumbar flexion, hip flexion, and plantar flexion experienced no remarkable changes between trials. These data provide insight as to how changing the load of the GM affects EMG activity, kinematic variables, and estimated hamstring length. Implications for hamstring injury prevention are discussed. More research is needed for further insight as to how load affects EMG activity and kinematics of other exercises.

The modified Thomas test was developed to assess the presence of hip flexion contracture and to measure hip extensibility. Despite its widespread use, to the authors’ knowledge, its criterion reference validity has not yet been investigated. The purpose of this study was to assess the criterion reference validity of the modified Thomas test for measuring peak hip extension angle and hip extension deficits, as defined by the hip not being able to extend to 0º, or neutral. Twenty-nine healthy college students (age = 22.00 ± 3.80 years; height = 1.71 ± 0.09 m; body mass = 70.00 ± 15.60 kg) were recruited for this study. Bland–Altman plots revealed poor validity for the modified Thomas test’s ability to measure hip extension, which could not be explained by differences in hip flexion ability alone. The modified Thomas test displayed a sensitivity of 31.82% (95% CI [13.86–54.87]) and a specificity of 57.14% (95% CI [18.41–90.10]) for testing hip extension deficits. It appears, however, that by controlling pelvic tilt, much of this variance can be accounted for (r = 0.98). When pelvic tilt is not controlled, the modified Thomas test displays poor criterion reference validity and, as per previous studies, poor reliability. However, when pelvic tilt is controlled, the modified Thomas test appears to be a valid test for evaluating peak hip extension angle.

Background: Use of synthetic cathinones, which are designer stimulants found in “bath salts,” has increased dramatically in recent years. Following governmental bans of methylenedioxypyrovalerone, mephedrone, and methylone, a second generation of synthetic cathinones with unknown abuse liability has emerged as replacements.

Methods: Using a discrete trials current intensity threshold intracranial self-stimulation procedure, the present study assessed the effects of 2 common second-generation synthetic cathinones, α‐pyrrolidinopentiophenone (0.1–5mg/kg) and 4-methyl-N-ethcathinone (1–100mg/kg) on brain reward function. Methamphetamine (0.1–3mg/kg) was also tested for comparison purposes.

Results: Results revealed both α‐pyrrolidinopentiophenone and 4-methyl-N-ethcathinone produced significant intracranial self-stimulation threshold reductions similar to that of methamphetamine. α‐Pyrrolidinopentiophenone (1mg/kg) produced a significant maximal reduction in intracranial self-stimulation thresholds (~19%) most similar to maximal reductions produced by methamphetamine (1mg/kg, ~20%). Maximal reductions in intracranial self-stimulation thresholds produced by 4-methyl-N-ethcathinone were observed at 30mg/kg (~15%) and were comparable with those observed with methamphetamine and α‐pyrrolidinopentiophenone tested at the 0.3-mg/kg dose (~14%). Additional analysis of the ED50 values from log-transformed data revealed the rank order potency of these drugs as methamphetamine ≈ α‐pyrrolidinopentiophenone>4-methyl-N-ethcathinone.

Conclusions: These data suggest that the newer second-generation synthetic cathinones activate the brain reward circuitry and thus may possess a similar degree of abuse potential as prototypical illicit psychostimulants such as methamphetamine as well as the first generation synthetic cathinone methylenedioxypyrovalerone, as previously reported.

The group I metabotropic glutamate receptors (mGluR1a and mGluR5) are important modulators of neuronal structure and function. Although these receptors share common signaling pathways, they are capable of having distinct effects on cellular plasticity. We investigated the individual effects of mGluR1a or mGluR5 activation on dendritic spine density in medium spiny neurons in the nucleus accumbens (NAc), which has become relevant with the potential use of group I mGluR based therapeutics in the treatment of drug addiction. We found that systemic administration of mGluR subtype-specific positive allosteric modulators had opposite effects on dendritic spine densities. Specifically, mGluR5 positive modulation decreased dendritic spine densities in the NAc shell and core, but was without effect in the dorsal striatum, whereas increased spine densities in the NAc were observed with mGluR1a positive modulation. Additionally, direct activation of mGluR5 via CHPG administration into the NAc also decreased the density of dendritic spines. These data provide insight on the ability of group I mGluRs to induce structural plasticity in the NAc and demonstrate that the group I mGluRs are capable of producing not just distinct, but opposing, effects on dendritic spine density.