Faculty and Staff

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.

Synthetic cathinones, colloquially referred to as “bath salts,” are derivatives of the psychoactive alkaloid cathinone found in Catha edulis (Khat). Since the mid-to-late 2000s, these amphetamine-like psychostimulants have gained popularity amongst drug users due to their potency, low cost, ease of procurement, and constantly evolving chemical structures. Concomitant with their increased use is the emergence of a growing collection of case reports of bizarre and dangerous behaviors, toxicity to numerous organ systems, and death. However, scientific information regarding the abuse liability of these drugs has been relatively slower to materialize. Recently we have published several studies demonstrating that laboratory rodents will readily self-administer the “first generation” synthetic cathinones methylenedioxypyrovalerone (MDPV) and methylone via the intravenous route, in patterns similar to those of methamphetamine. Under progressive ratio schedules of reinforcement, the rank order of reinforcing efficacy of these compounds is MDPV ≥ methamphetamine > methylone. MDPV and methylone, as well as the “second generation” synthetic cathinones α-pyrrolidinovalerophenone (α-PVP) and 4-methylethcathinone (4-MEC), also dose-dependently increase brain reward function. Collectively, these findings indicate that synthetic cathinones have a high abuse and addiction potential and underscore the need for future assessment of the extent and duration of neurotoxicity induced by these emerging drugs of abuse.

The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first 2 weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, and amphetamine. However, no studies have yet examined the effects of MS on methamphetamine (METH) SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, we also investigated group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) core. Long–Evans pups and dams were separated on postnatal days (PND) 2–14 for either 180 (MS180) or 15 min (MS15). Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion) in 15 2-h daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.

We study the so-called Descent, or [bar over Q], Equation for the null polygonal supersymmetric Wilson loop in the framework of the pentagon operator product expansion. To properly address this problem, one requires to restore the cyclicity of the loop broken by the choice of OPE channels. In the course of the study, we unravel a phenomenon of twist enhancement when passing to a cyclically shifted channel. Currently, we focus on the consistency of the all-order Descent Equation for the particular case relating the NMHV heptagon to MHV hexagon. We find that the equation establishes a relation between contributions of different twists and successfully verify it in perturbation theory making use of available bootstrap predictions for elementary pentagons.

Background: 5-HT1B receptor agonists enhance cocaine intake during daily self-administration sessions but decrease cocaine intake when tested after prolonged abstinence. We examined if 5-HT1B receptor agonists produce similar abstinence-dependent effects on methamphetamine intake.

Methods: Male rats were trained to self-administer methamphetamine (0.1 mg/kg, i.v.) on low (fixed ratio 5 and variable ratio 5) and high (progressive ratio) effort schedules of reinforcement until intake was stable. Rats were then tested for the effects of the selective 5-HT1B receptor agonist, CP 94,253 (5.6 or 10 mg/kg), or the less selective but clinically available 5-HT1B/1D receptor agonist, zolmitriptan (10 mg/kg), on methamphetamine self-administration both before and after a 21-day forced abstinence period during which the rats remained in their home cages.

Results: The inverted U-shaped, methamphetamine dose-response function for intake on the fixed ratio 5 schedule was shifted downward by CP 94,253 both before and after abstinence. The CP 94,253-induced decrease in methamphetamine intake was replicated in rats tested on a variable ratio 5 schedule, and the 5-HT1B receptor antagonist SB 224,289 (10 mg/kg) reversed this effect. CP 94,253 also attenuated methamphetamine intake on a progressive ratio schedule both pre- and postabstinence. Similarly, zolmitriptan attenuated methamphetamine intake on a variable ratio 5 schedule both pre- and postabstinence, and the latter effect was sustained after each of 2 more treatments given every 2 to 3 days prior to daily sessions.

Conclusions: Unlike the abstinence-dependent effect of 5-HT1B receptor agonists on cocaine intake reported previously, both CP 94,253 and zolmitriptan decreased methamphetamine intake regardless of abstinence. These findings suggest that 5-HT1B receptor agonists may have clinical efficacy for psychostimulant use disorders.

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.

We present a new approach to computing event shape distributions or, more precisely, charge flow correlations in a generic conformal field theory (CFT). These infrared finite observables are familiar from collider physics studies and describe the angular distribution of global charges in outgoing radiation created from the vacuum by some source. The charge flow correlations can be expressed in terms of Wightman correlation functions in a certain limit. We explain how to compute these quantities starting from their Euclidean analogues by means of a nontrivial analytic continuation which, in the framework of CFT, can be performed elegantly in Mellin space. The relation between the charge flow correlations and Euclidean correlation functions can be reformulated directly in configuration space, bypassing the Mellin representation, as a certain Lorentzian double discontinuity of the correlation function integrated along the cuts. We illustrate the general formalism in N = 4 SYM, making use of the well-known results on the four-point correlation function of half-BPS scalar operators. We compute the double scalar flow correlation in N = 4 SYM, at weak and strong coupling and show that it agrees with known results obtained by different techniques. One of the remarkable features of the N = 4 theory is that the scalar and energy flow correlations are proportional to each other. Imposing natural physical conditions on the energy flow correlations (finiteness, positivity and regularity), we formulate additional constraints on the four-point correlation functions in N = 4SYM that should be valid at any coupling and away from the planar limit.

We analyze the near-collinear limit of the null polygonal hexagon super Wilson loop in the planar N = 4 super-Yang–Mills theory. We focus on its Grassmann components which are dual to next-to-maximal helicity-violating (NMHV) scattering amplitudes. The kinematics in question is studied within a framework of the operator product expansion that encodes propagation of excitations on the background of the color flux tube stretched between the sides of Wilson loop contour. While their dispersion relation is known to all orders in 't Hooft coupling from previous studies, we find their form factor couplings to the Wilson loop. This is done making use of a particular tessellation of the loop where pentagon transitions play a fundamental role. Being interested in NMHV amplitudes, the corresponding building blocks carry a nontrivial charge under the SU(4) R-symmetry group. Restricting the current consideration to twist-two accuracy, we analyze two-particle contributions with a fermion as one of the constituents in the pair. We demonstrate that these nonsinglet pentagons obey bootstrap equations that possess consistent solutions for any value of the coupling constant. To confirm the correctness of these predictions, we calculate their contribution to the super Wilson loop demonstrating agreement with recent results to four-loop order in 't Hooft coupling.

We study event shapes in N = 4SYM describing the angular distribution of energy and R-charge in the final states created by the simplest half-BPS scalar operator. Applying the approach developed in the companion paper arXiv:1309.0769, we compute these observables using the correlation functions of certain components of the N = 4 stress-tensor supermultiplet: the half-BPS operator itself, the R-symmetry current and the stress tensor. We present master formulas for the all-order event shapes as convolutions of the Mellin amplitude defining the correlation function of the half-BPS operators, with a coupling-independent kernel determined by the choice of the observable. We find remarkably simple relations between various event shapes following from N = 4 superconformal symmetry. We perform thorough checks at leading order in the weak coupling expansion and show perfect agreement with the conventional calculations based on amplitude techniques. We extend our results to strong coupling using the correlation function of half-BPS operators obtained from the AdS/CFT correspondence.

We compute one-loop renormalization group equations for non-singlet twist-four operators in QCD. The calculation heavily relies on the light-cone gauge formalism in the momentum fraction space that essentially rephrases the analysis of all two-to-two and two-to-three transition kernels to purely algebraic manipulations both for non- and quasipartonic operators. This is the first brute force calculation of this sector available in the literature. Fourier transforming our findings to the coordinate space, we checked them against available results obtained within a conformal symmetry-based formalism that bypasses explicit diagrammatic calculations and confirmed agreement with the latter.