Effects of auditory and thermal stimuli on 3,4- methylenedioxymethamphetamine (MDMA)-induced neurochemical and behavioral responses

textThe amphetamine derivative, 3,4-methylenedioxymethamphetamine (MDMA), is a popular drug often taken by young adults at dance clubs or rave parties. Laser light shows, fast-paced electronic music, and hot crowded dance floors are characteristic of these events, and Ecstasy users report that the acute effects of the drug are potentiated by these stimulatory conditions. However, it remains largely unknown how environmental stimuli impact the neurochemical and physiological effects of MDMA. The aim of the first study presented in this dissertation was to investigate how auditory stimuli (music, white noise, and no additional sound) influence MDMA conditioned place preference (CPP), self-administration, and nucleus accumbens (NAcc) dopamine (DA) and serotonin (5-HT) responses. Findings revealed a significant CPP for animals exposed to white noise during MDMA conditioning trials. After self-administration of MDMA (1.5 mg/kg), NAcc DA and 5-HT were highest in rats exposed to music during the test session. The second study aimed to investigate the effects of ambient temperature (23°or 32°C) on long-term MDMA self-administration and neurochemical responses. Results indicated no difference in self-administration or locomotor activity rates for the high versus room temperature groups across sessions. However, MDMA (3.0 mg/kg) administered in high ambient temperature resulted in significantly greater NAcc serotonin release compared to when taken at room temperature, but no differences in dopamine response was determined between the two conditions. Overall, these results indicate that auditory and thermal stimuli can effect MDMA-induced behavioral and neurochemical responses. The last aim tested a novel apparatus and method for use in animal models of drug reinforcement. By combining traditional CPP and self-administration procedures, this approach provided more informative data and circumvented some inherent drawbacks of each method alone. In addition to confirming the ability to produce drug conditioned place preferences after short- and long-term experiments, the long-term version of the procedure revealed a significant positive relationship between lever response rate and CPP magnitude. Therefore, this experimental design can be used to identify subgroups of rats that may vary in sensitivity to drug motivational effects. Further study of these populations may be useful in the development of behavioral and pharmacological therapies for drug addiction.Pharmac

Neuronal nicotinic acetylcholine receptors: neuroplastic changes underlying alcohol and nicotine addictions

Addictive drugs can activate systems involved in normal reward-related learning, creating long-lasting memories of the drug's reinforcing effects and the environmental cues surrounding the experience. These memories significantly contribute to the maintenance of compulsive drug use as well as cue-induced relapse which can occur even after long periods of abstinence. Synaptic plasticity is thought to be a prominent molecular mechanism underlying drug-induced learning and memories. Ethanol and nicotine are both widely abused drugs that share a common molecular target in the brain, the neuronal nicotinic acetylcholine receptors (nAChRs). The nAChRs are ligand-gated ion channels that are vastly distributed throughout the brain and play a key role in synaptic neurotransmission. In this review, we will delineate the role of nAChRs in the development of ethanol and nicotine addiction. We will characterize both ethanol and nicotine's effects on nAChR-mediated synaptic transmission and plasticity in several key brain areas that are important for addiction. Finally, we will discuss some of the behavioral outcomes of drug-induced synaptic plasticity in animal models. An understanding of the molecular and cellular changes that occur following administration of ethanol and nicotine will lead to better therapeutic strategies

NEUROCHEMICAL AND BEHAVIORAL RESPONSES

approved version of the following dissertation

MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial

Cognitive-behavioural conjoint therapy (CBCT) for PTSD has been shown to improve PTSD, relationship adjustment, and the health and well-being of partners. MDMA (3,4-methylenedioxymethamphetamine) has been used to facilitate an individual therapy for PTSD. This study was an initial test of the safety, tolerability, and efficacy of MDMA-facilitated CBCT. Six couples with varying levels of baseline relationship satisfaction in which one partner was diagnosed with PTSD participated in a condensed version of the 15-session CBCT protocol delivered over 7 weeks. There were two sessions in which both members of the couple were administered MDMA. All couples completed the treatment protocol, and there were no serious adverse events in either partner. There were significant improvements in clinician-assessed, patient-rated, and partner-rated PTSD symptoms (pre- to post-treatment/follow-up effect sizes ranged from d = 1.85–3.59), as well as patient depression, sleep, emotion regulation, and trauma-related beliefs. In addition, there were significant improvements in patient and partner-rated relationship adjustment and happiness (d =.64–2.79). These results are contextualized in relation to prior results from individual MDMA-facilitated psychotherapy and CBCT for PTSD alone. MDMA holds promise as a facilitator of CBCT to achieve more robust and broad effects on individual and relational functioning in those with PTSD and their partners