Matthew E. Andrzejewski

Interactions between the CB1 receptor agonist Δ9-THC and the CB1 receptor antagonist SR-141716 in rats: Open-field revisited

This study examined the effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and the CB1 antagonist SR-141716 on open-field behaviors in male Sprague-Dawley rats. Animals were examined after administration of Delta(9)-THC alone (dose range: 0.3-5.6 mg/kg), SR-141716 alone (dose range: 1-5.6 mg/kg) and the two drugs in combination; injections were given intraperitoneally 30 min prior to testing. There was a dose-related suppression of ambulation (horizontal activity) and rearing (vertical activity) after Delta(9)-THC administration. Co-administration of SR-141716 counteracted this suppression; however, antagonism was only partial for rearing. Interestingly, 1 mg/kg SR-141716 was as effective as 3 and 5.6 mg/kg SR-141716 in this antagonist action. Increasing doses of Delta(9)-THC produced an increase in circling behavior; latency to leave the starting area in the center of the field was significantly elevated by 5.6 mg/kg Delta(9)-THC. Those effects were completely blocked by SR-141716. Grooming and scratching showed a dose-related increase following administration of SR-141716 (1-5.6 mg/kg), which were only partially blocked by co-administration of Delta(9)-THC (3 and 5.6 mg/kg). When given alone, only the highest dose of SR-141716 (5.6 mg/kg) depressed ambulation; rearing and latency were not significantly changed, and circling was absent. Differences in the number of vocalizations, urination and defecation generally did not differ clearly among the treatment conditions. These results may show that SR-141716 is acting as (i) an inverse agonist and/or (ii) that the endogenous cannabinoid system is tonically active under certain conditions.

A comparison of adult and adolescent rat behavior in operant learning, extinction, and behavioral inhibition paradigms.

Poor self-control, lack of inhibition, and impulsivity contribute to the propensity of adolescents to engage in risky or dangerous behaviors. Brain regions (e.g., prefrontal cortex) involved in impulse-control, reward-processing, and decision-making continue to develop during adolescence, raising the possibility that an immature brain contributes to dangerous behavior during adolescence. However, very few validated animal behavioral models are available for behavioral neuroscientists to explore the relationship between brain development and behavior. To that end, a valid model must be conducted in the relatively brief window of adolescence and not use manipulations that potentially compromise development. The present experiments used three operant arrangements to assess whether adolescent rats differ from adults in measures of learning, behavioral inhibition, and impulsivity, within the aforementioned time frame without substantial food restriction. In Experiment 1, separate squads of rats were trained to lever-press and then transitioned to two types of extinction. Relative to their baselines, adolescent rats responded more during extinction than adults, suggesting that they were less sensitive to the abolishment of the reinforcement contingency. Experiment 2 demonstrated similar age-related differences during exposure to a differential reinforcement of low rates schedule, a test of behavioral inhibition. Lastly, in Experiment 3, adolescents responding decreased more slowly than adults during exposure to a resetting delay of reinforcement schedule, suggesting impaired self-control. Results from these experiments suggest that adolescents exhibit impaired learning, behavioral inhibition and self-control, and in concert with recent reports, provide researchers with three behavioral models to more fully explore neurobiology of risk-taking behavior in adolescence.

Technology transfer through performance management: the effects of graphical feedback and positive reinforcement on drug treatment counselors’ behavior

After drug treatment counselors at a community-based methadone treatment clinic were trained in implementing a contingency management (CM) intervention, baseline measures of performance revealed that, on average, counselors were meeting the performance criteria specified by the treatment protocol about 42% of the time. Counselors were exposed to graphical feedback and a drawing for cash prizes in an additive within-subjects design to assess the effectiveness of these interventions in improving protocol adherence. Counselor performance measures increased to 71% during the graphical feedback condition, and to 81% during the drawing. Each counselors performance improved during the intervention conditions. Additional analyses suggested that counselors did not have skill deficits that hindered implementation. Rather, protocol implementation occurred more frequently when consequences were added, thereby increasing the overall proportion of criteria met. Generalizations, however, may be limited due to a small sample size and possible confounding of time and intervention effects. Nonetheless, present results show promise that feedback and positive reinforcement could be used to improve technology transfer of behavioral interventions into community clinic settings.

Ethanol consumption and the matching law: a choice analysis using a limited-access paradigm

Choice analyses, especially R. J. Herrnsteins (1961, 1970) matching law, have recently been extended to substance abuse and drug research. The experiment reported here used a limited-access paradigm to engender ethanol consumption in Sprague-Dawley rats (Rattus norvegicus). After stable ethanol consumption was established, several 2-bottle choice tests were run. Relative volumes of solutions consumed were compared to relative ethanol concentrations as an application of the matching law. The formula for the generalized matching law confirmed that although biases varied, they were small, and more important, sensitivities to the relative concentrations were positive in 24 of 28 subjects. The results also revealed a high positive correlation between baseline ethanol consumption (g/kg) and subsequently assessed sensitivity. Overall, these findings suggest that a matching law analysis can be useful for examining ethanol intake in randomly bred rats.

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

Opioid transmission and dysregulated prefrontal cortex (PFC) activity have both been implicated in the inhibitory-control deficits associated with addiction and binge-type eating disorders. What remains unknown, however, is whether endogenous opioid transmission within the PFC modulates inhibitory control. Here, we compared intra-PFC opioid manipulations with a monoamine manipulation (d-amphetamine), in two sucrose-reinforced tasks: progressive ratio (PR), which assays the motivational value of an incentive, and differential reinforcement of low response rates (DRLs), a test of inhibitory control. Intra-PFC methylnaloxonium (M-NX, a limited diffusion opioid antagonist) was given to rats in a ‘low-drive’ condition (2-h food deprivation), and also after a motivational shift to a ‘high-drive’ condition (18-h food deprivation). Intra-PFC DAMGO (D-[Ala2,N-MePhe4, Gly-ol]-enkephalin; a μ-opioid agonist) and d-amphetamine were also tested in both tasks, under the low-drive condition. Intra-PFC M-NX nearly eliminated impulsive action in DRL engendered by hunger, at a dose (1 μg) that significantly affected neither hunger-induced PR enhancement nor hyperactivity. At a higher dose (3 μg), M-NX eliminated impulsive action and returned PR breakpoint to low-drive levels. Conversely, intra-PFC DAMGO engendered ‘high-drive-like’ effects: enhancement of PR and impairment of DRL performance. Intra-PFC d-amphetamine failed to produce effects in either task. These results establish that endogenous PFC opioid transmission is both necessary and sufficient for the expression of impulsive action in a high-arousal, high-drive appetitive state, and that PFC-based opioid systems enact functionally unique effects on food impulsivity and motivation relative to PFC-based monoamine systems. Opioid antagonists may represent effective treatments for a range of psychiatric disorders with impulsivity features.

Is extinction the hallmark of operant discrimination?: Reinforcement and SΔ effects

Using a successive discrimination procedure with rats, three experiments investigated the contribution of reinforcement rate and amount of SΔ exposure on the acquisition of an operant discrimination. SD components and were always 2 min in length, while SΔ (extinction) components were either 1 min or 4 min in length; responses in SD were reinforced on one of four schedules. In Experiment 1, each of eight groups were exposed to one possible combination of rate of reinforcement and SΔ component length. At every level of reinforcement, the 4 min SΔ groups acquired the discrimination more quickly. However, within each level of reinforcement, the proportions of responding in SD as a function cumulative SΔ exposure were equivalent, regardless of the number of reinforcers earned in SD, suggesting that extinction is the “hallmark” of discrimination. Experiment 2 sought to replicate these results in a within-subjects design, and although the 4 min SΔ conditions always produced superior discriminations, the lack of discriminated responding in some conditions suggested that stimulus disparity was reduced. Experiment 3 clarified those results and extended the finding that the acquisition of operant discrimination closely parallels extinction of responding in SΔ. In sum, it appears that higher reinforcement rates and longer SΔ exposure facilitate the acquisition of discriminated operant responding.