Investigation of the reinforcing potential of samidorphan and naltrexone by fixed and progressive ratio intravenous self-administration testing in heroin-maintained rats

Background: Samidorphan is a novel μ-opioid antagonist with low intrinsic activity at κ- and δ-opioid receptors. Aims: Because samidorphan is central nervous system-active, we investigated whether samidorphan (13.6, 40.8, 68 μg/kg/injection) served as a positive reinforcer in rats trained to self-administer heroin on a fixed ratio-5 schedule. Samidorphan’s relative reinforcing effect was evaluated by progressive ratio/break-point determination. Naltrexone (13.6, 40.8, 68 μg/kg/injection) and heroin (7.5, 15, 25 μg/kg/injection) were comparators. Results: All heroin doses maintained self-administration on fixed ratio-5 and progressive ratio/break-points at levels significantly greater than saline. Samidorphan and naltrexone had similar profiles on fixed ratio-5 with one samidorphan dose serving as a positive reinforcer and one naltrexone dose showing a strong trend ( p=0.053) for positive reinforcement. The numbers of injections of every samidorphan and naltrexone dose were significantly lower than all heroin doses. The numbers of self-administered samidorphan and naltrexone injections/session on fixed ratio-5 were not significantly different from one another. The mean inter-injection intervals for heroin were significantly shorter than for saline, whereas those of samidorphan and naltrexone were not. Progressive ratio break-points for samidorphan and naltrexone were not different from saline except for the highest dose of samidorphan. In addition, the progressive ratio break-points for samidorphan were not significantly different from those of naltrexone and were significantly lower than heroin. The samidorphan unit-doses evaluated in self-administration yielded plasma concentrations ranging between 25–109% and 10–45% of the maximum concentration values in humans. Conclusions: Overall, the profiles of samidorphan and naltrexone, which has no abuse liability, were similar in this model.

METODE TOTAL TASK PRESENTATION CHAINING PADA ANAK DENGAN INTELLECTUAL DISABILITY-SEVERE

Tujuan dari pelaksanaan program modifikasi perilaku ini adalah untuk meningkatkan kemampuan A, anak laki-laki berusia 6 tahun 9 bulan dengan intellectual disability-severe dalam memakai baju kaos tanpa kancing secara mandiri. Kondisi A saat ini belum dapat berbicara, tidak paham pemberian instruksi secara verbal, dan tidak dapat berpakaian sendiri. Metode modifikasi perilaku yang digunakan adalah total task presentation chaining yang disertai dengan pemberian prompt dan positive reinforcer. Prompt yang digunakan adalah video prompt, verbal prompt, gestural/ modeling prompt, dan physical prompt. Chain dari perilaku memakai baju kaos terdiri dari 4 langkah sederhana yang disesuaikan dengan kemampuan kognitif serta fisik A saat ini. Program modifikasi perilaku ini dapat dikatikan berhasil. Setelah melakukan 8 sesi dengan 3 kali latihan setiap sesi, A dapat melakukan 4 langkah tanpa bantuan orang lain. Kemampuan tersebut dikatakan konsisten dari data follow up yang dilakukan 1 minggu setelah sesi berakhir.

Nadsat: The oscillation between reader immersion and repulsion

This article explores the oscillation between immersion and repulsion amongst readers of A clockwork orange by Anthony Burgess. I argue that nadsat, as an invented language, introduces the state of ‘reader immersion’ resulting in ‘flow’ by means of a ‘ludic reading’ motivational structure. Reader curiosity acts as a ‘positive reinforcer’ through the sense of accomplishment felt by mastering nadsat. Reader repulsion occurs once nadsat is understood. Repulsion is induced as a result of the brutality the nadsat narrative communicates. However, repulsion does not necessarily cause the reader to stop reading, but rather acts as a sensationally derived motivation to continue reading. This type of motivation is identified as a ‘negative reinforcer’. Both motivational structures (positive and negative reinforcers) develop the oscillation between reader immersion and repulsion as part of the reading experience A clockwork orange offers. The aim of this article is to discuss the oscillation between immersion and repulsion experienced by readers of A clockwork orange according to the theoretical frameworks indicated above.