Perceived Ability to Treat Opioid Use Disorder in West Virginia.

Introduction: Medication-assisted treatment (MAT) is an evidence-based therapy for opioid use disorder (OUD) that has not been fully implemented in rural areas due to patient, provider, and logistical barriers. Limited information is available on provider perceptions of barriers to MAT in rural Central Appalachia which has very high rates of OUD compared to the rest the United States. Purpose: Determine perceived barriers for potential prescribers to using MAT, including buprenorphine, as part of treatment for OUD in West Virginia. Methods: A 30-question, anonymous survey was sent to physicians, physician assistants and advanced practice registered nurses using an online link. Link was distributed through the WV Medicaid provider list, professional association and institutional contact lists, and social media. Comparisons were made by provider waivered or non-waivered status. Results: Overall, 84% of waivered providers (n = 77) and only 8% of non-waivered providers (n = 341) indicated ever prescribing a form of MAT for OUD; 73% percent of waivered providers were currently prescribing MAT and accepting new patients with OUD. Only 4% of non-waivered providers were currently prescribing MAT and 21% were currently accepting new patients with OUD. Lack of available mental health and psychosocial support services and concerns about diversion or misuse of medication were the top perceived barriers to implementing MAT programs. Implications: Implementing strategies to improve access to behavioral health care including telehealth and apps, provider training and addressing stigma around OUD treatment were identified as priorities that would help increase providers' willingness to prescribe medications for OUD treatment.

The effect of nicotine on sign-tracking and goal-tracking in a Pavlovian conditioned approach paradigm in rats.

RATIONALE: Nicotine (NIC) potently increases operant responding for non-NIC reinforcers, and this effect may depend on drug-mediated increases in incentive motivation. According to this hypothesis, NIC should also potently increase approach to Pavlovian-conditioned stimuli associated with rewards. OBJECTIVE: The present studies explored the effects of NIC on Pavlovian-conditioned approach responses. METHOD: To do so, liquid dippers were used to deliver an unconditioned stimulus (US; 0.1 ml sucrose) after presentation of a conditioned stimulus (CS; 30 s illumination of a stimulus light)-both the CS and US were presented in receptacles equipped to monitor head entries. RESULTS: In experiment 1, the CS and US were presented in the same receptacle, but NIC pretreatment (0.4 mg/kg base) did not increase conditioned approach responses. Delivery of the sucrose US was then shifted to receptacle in a different location. All rats learned to approach the new US location (goal-tracking) at similar rates. Approach to the CS receptacle (sign-tracking) declined for saline-pretreated rats, but NIC pretreatment increased sign-tracking. In experiment 2, NIC pretreatment increased sign-tracking when the CS and US were spatially separated during acquisition. In experiment 3, NIC pretreatments were replaced with saline, but the effect of NIC persisted for an additional 24 test sessions. CONCLUSION: The findings suggest that NIC increases incentive motivation and that this effect is long-lasting, persisting beyond the pharmacological effects of NIC.

Sex and dose-related differences in methylphenidate adolescent locomotor sensitization and effects on brain-derived neurotrophic factor.

This study analyzed repeated methylphenidate (MPH) administration and its effects on brain-derived neurotrophic factor (BDNF) in the dorsal striatum and nucleus accumbens of male and female adolescent rats. In Experiment 1, rats were administered intraperitoneal (ip) saline, 1, 3, or 5 mg/kg dose of MPH every second day from postnatal day (P)33-P49. Locomotor activity was analyzed for 10 min after each administration. Results revealed that the 1 mg/kg dose of MPH produced locomotor suppression, however, the 5 mg/kg dose of MPH produced locomotor sensitization and robust behavioral activation in females as compared to males. In Experiment 2, animals were administered ip saline or the 5 mg/kg dose of MPH using an identical regimen but a 30 min behavioral test was employed. Dorsal striatum and nucleus accumbens tissue was assayed for BDNF at P50. Females demonstrated sensitization to MPH and increased locomotor activation compared to males. Interestingly, females given MPH demonstrated a significant 42% decrease of striatal BDNF whereas males administered MPH demonstrated a significant 50.4% increase of striatal BDNF compared to controls. There were no effects on accumbal BDNF. This report demonstrates robust sex differences in the behavioral response, but sex-dependent changes in striatal BDNF in response to MPH in adolescence.

Schizophrenia and substance abuse comorbidity: nicotine addiction and the neonatal quinpirole model.

This review focuses on nicotine comorbidity in schizophrenia, and the insight into this problem provided by rodent models of schizophrenia. A particular focus is on age differences in the response to nicotine, and how this relates to the development of the disease and difficulties in treatment. Schizophrenia is a particularly difficult disease to model in rodents due to the fact that it has a plethora of symptoms ranging from paranoia and delusions of grandeur to anhedonia and negative affect. The basis of these symptoms is believed to be due to neurochemical abnormalities and neuropathology in the brain, which most models have attempted to emulate. A brief review of findings regarding nicotine use and abuse in schizophrenics is presented, with findings using rodent models that have been able to provide insight into the mechanisms of addiction. A common clinical approach to the treatment of nicotine addiction in the schizophrenic population has been that these drugs are used for self-medication purposes, and it is clear that self-medication may actually be directed at several symptoms, including cognitive impairment and anhedonia. Finally, our laboratory has reported across a series of studies that neonatal treatment with the dopamine D(2)/D(3) receptor agonist quinpirole results in long-term increases in dopamine-like receptor sensitivity, consistent with data reporting increases in dopamine D(2) receptor function in schizophrenia. Across these studies, we have reported several behavioral, neurochemical, and genetic consistencies with the disease, and present a hypothesis for what we believe to be the basis of psychostimulant addiction in schizophrenia.

Neonatal quinpirole treatment enhances locomotor activation and dopamine release in the nucleus accumbens core in response to amphetamine treatment in adulthood.

Neonatal quinpirole treatment to rats produces long-term increases in D(2) receptor sensitivity that persists throughout the animal's lifetime, a phenomenon referred to as D(2) priming. Male and female Sprague-dawley rats were administered quinpirole (1 mg kg(-1)) or saline from postnatal days (P)1-11. At P60, all animals were given an injection of quinpirole (100 microg kg(-1)), and results showed that rats neonatally treated with quinpirole demonstrated enhanced yawning in response to quinprole, verifying D(2) receptor priming because yawning is a D(2) receptor mediated event. Beginning 1-3 days later, locomotor sensitization was tested through administration of d-amphetamine (1 mg kg(-1)) or saline every other day over 14 days, and horizontal activity and turning behavior were analyzed. Findings indicated that D(2)-priming enhanced horizontal activity in response to amphetamine in females compared to males at Days 1 and 4 of locomotor sensitization testing, and D(2)-priming enhanced turning in response to amphetamine. Seven to ten days after sensitization was complete, microdialysis of the NAcc core was performed using a cumulative dosing regimen of amphetamine (0.1-3.0 mg kg(-1)). D(2)-primed rats administered amphetamine demonstrated a 500% increase in accumbal DA overflow compared to control rats administered amphetamine. Additionally, amphetamine produced a significant increase in NE overflow compared to controls, but this was unaffected by D(2) priming. These results indicate that D(2) receptor priming as is produced by neonatal quinpirole treatment robustly enhances behavioral activation and accumbal DA overflow in response to amphetamine, which may underlie increases in psychostimulant use and abuse within the psychotic population where increased D(2) receptor sensitivity is a hallmark.

Nicotine sensitization and analysis of brain-derived neurotrophic factor in adolescent beta-arrestin-2 knockout mice.

Nicotine sensitization and levels of brain-derived neurotrophic factor (BDNF) were analyzed in adolescent beta-arrestin-2 knockout (betaA-2 KO) and wild type (WT) mice. The beta-arrestin-2 protein has been shown to be important in G-protein hydrolysis and receptor internalization. Four- to five-week-old adolescent betaA-2 KO and WT C57/Bl6 mice were administered either nicotine (0.5 mg/kg free base) or saline 10 min before being placed into a locomotor arena on each of 7 (Experiment 1) or 14 (Experiment 2) consecutive days. A nicotine challenge was given 7 days after sensitization was complete. In Experiment 1, betaA-2 KO mice administered nicotine or saline and WT mice administered nicotine demonstrated significant hypoactivity during early in testing, and neither WT nor betaA-2 KO mice administered nicotine demonstrated sensitization. On the nicotine challenge, WT mice administered nicotine demonstrated significantly higher activity levels compared to all groups, and this same group demonstrated significantly higher levels of accumbal BDNF compared to all groups. In Experiment 2, betaA-2 KO mice were again hypoactive compared to WT mice, whereas WT mice administered nicotine demonstrated significant hypoactivity during initial testing and significantly higher levels of activity compared to all other groups late in testing. On the nicotine challenge, WT mice that received nicotine demonstrated a significant increase in activity compared to all groups, and showed increased accumbal BDNF compared to all groups. These results show that the beta-arrestin-2 protein is important in induction and expression of nicotine sensitization as well as nicotine's effects on accumbal BDNF.