Brief and extended abstinence from chronic oral methylphenidate treatment produces reversible behavioral and physiological effects.

Methylphenidate (MP) is a commonly prescribed psychostimulant to individuals with Attention Deficit Hyperactivity Disorder, and is often used illicitly among healthy individuals with intermittent breaks to coincide with breaks from school. This study examined how intermittent abstinence periods impact the physiological and behavioral effects of chronic oral MP self-administration in rats, and whether these effects persist following prolonged abstinence from the drug. Rats were treated orally with water, low-dose (LD), or high-dose (HD) MP, beginning at PND 28. This daily access continued for three consecutive weeks followed by a 1-week abstinence; after three repeats of this cycle, there was a 5-week abstinence period. Throughout the study, we examined body weight, food intake, locomotor activity, and anxiety- and depressive-like behaviors. During the treatment phase, HD MP decreased body weight, food intake, and depressive- and anxiety-like behaviors, while it increased locomotor activity. During intermittent abstinence, the effects of MP on locomotor activity were eliminated. During prolonged abstinence, most of the effects of HD MP were ameliorated to control levels, with the exception of weight loss and anxiolytic effects. These findings suggest that intermittent exposure to chronic MP causes physiological and behavioral effects that are mostly reversible following prolonged abstinence.

Neuroendocrine regulation of pubertal suppression in the naked mole-rat: What we know and what comes next.

Puberty is a key developmental milestone that marks an individual's maturation in several ways including, but not limited to, reproductive maturation, changes in behaviors and neural organization. The timing at which puberty occurs is variable both within individuals of the same species and between species. These variations can be aligned with ecological cues that delay or suppress puberty. Naked mole-rats are colony-living rodents where reproduction is restricted to a few animals; all other animals are pubertally-suppressed. Animals removed from suppressive colony cues can reproductively mature, presenting the unique opportunity to study adult-onset puberty. Recently, we found that RFRP-3 administration sustains pubertal delay in naked mole-rats removed from colony. In this review, we explore what is known about regulators that control puberty onset, the role of stress/social status in pubertal timing, the status of knowledge of pubertal suppression in naked mole-rats and what comes next.

Weekday-only chronic oral methylphenidate self-administration in male rats: Reversibility of the behavioral and physiological effects.

Methylphenidate (MP) is a commonly prescribed psychostimulant for Attention Deficit Hyperactivity Disorder (ADHD). We recently reported behavioral and developmental effects of chronic MP use in healthy rats. The current study investigated how interrupting chronic MP treatment with weekend abstinence altered the behavioral and physiological consequences of chronic MP treatment, and if prolonged abstinence would reverse the observed effects. Male Sprague Dawley rats were assigned to one of three treatment groups: water (W); low dose (LD) MP; and high dose (HD) MP. For 13 weeks, rats had access to drink from a bottle containing 4 mg/kg MP (LD), 30 mg/kg MP (HD) or water (W) for 1 h, and 10 mg/kg MP (LD), 60 mg/kg MP (HD) or water (W) for the next 7 h, each week day. During weekends, all animals received only water as well as throughout the 5-week-long abstinence phase, which immediately followed the treatment phase. Throughout the treatment phase, regardless of weekend abstinence, chronic MP resulted in significant decreased food and fluid intake and body weight. Also, HD MP exposure resulted in the following behavioral effects: increased open field and circadian locomotor activity; increased latency to immobility and decreased time spent immobile in the forced swim test; increased center activity in the open field and percent of time spent in an open arm of the elevated-plus-maze; and increased social affiliation and memory in the Crawley's three chamber sociability test. During the prolonged (5-week) abstinence phase, all these effects were reversed while HD treated rats increased their fluid intake. These results indicated that intermittent brief abstinence periods (weekend's off-treatment) produced the same behavioral and developmental effects as those previously reported with chronic (7 days/week) MP treatment, but were reversible following a prolonged abstinence period (5 weeks).