Effect of three different regimens of repeated methamphetamine on rats’ cognitive performance

Abstract

Neurocognitive impairment in response to methamphetamine (MA) has been proven in a variety of experimental and clinical studies. Elucidation of the underlying mechanisms of MA-induced cognitive deficits and finding preventive/therapeutic approaches need best-suited animal models. In modeling repeated MA exposure, while some believes that escalating doses simulate drug abuse conditions, others believe this regimen confers a preconditioning protection. The present study aimed to compare the effects of three different regimens of repeated MA administration on memory and cognitive function of adult rats. Rats in two different experimental groups were treated with escalating paradigms consisted of twice-daily i.p. injections; 1-4 mg/kg over 7 days or 1-10 mg/kg over 10 days. The third group received twice-daily doses of 15 mg/kg every other day over 14 days. Spatial working memory, novel object recognition task and anxiety-like behavior were measured sequentially in all MA-treated rats and vehicle-treated controls started from day 8 after last injection. All MA regimens decreased rates of spontaneous alternation in Y-maze and increased anxiety-like response. Short-term recognition memory was unchanged across all MA-treated animals, while long-term memory was impaired in the second and third MA regimen. Though MA deleterious effect especially in recognition memory is somehow dose dependent, preconditioning effect of increasing doses may be ruled out at least in the case of parameters measured here.

Prelimbic cortex dynorphin/κ opioid receptor system modulates methamphetamine‐induced cognitive impairment

“…Since METH exposure can also lead to poor performances in other cognitive phenotypes, 35,37–39 we also conducted a Y‐maze test to further confirm the neuroprotective effects of KOR antagonist (Figure 7A,B). We found that METH decreased number (Figure 7E, F (2, 33) = 6.921, p = 0.0031) and rate of spontaneous alteration (SAP) (Figure 7F, F (2, 33) = 13.33, p < 0.0001) and increased incorrect same arms returns (SAR) (Figure 7D, F ((2, 33) = 4.995, p = 0.0127), which was reserved by norBNI microinjections into PL before METH treatment.…”

“…After 24 h of last METH injections, a Y‐maze spontaneous alternation behaviour test (SAB) was conducted to assess the spatial memory of mice 35 . The Y‐maze consisted of three identical Plexiglas arms (30 cm length × 6 cm width × 15 cm height), labelled A, B, C and orientated at 120° angles from each other.…”

“…Since METH exposure can also lead to poor performances in other cognitive phenotypes, 35,[37][38][39] we also conducted a Y-maze test to further confirm the neuroprotective effects of KOR antagonist (Figure 7A,B). We found that METH decreased number (Figure 7E, F The medial prefrontal cortex (mPFC) is a crucial brain region involved in cognition.…”

Effects of Molecular Hydrogen on Methamphetamine-Induced Neurotoxicity and Spatial Memory Impairment

“…Among the current illicit drugs, METH is the most prevalent illicit drug in numerous countries, including China (Bramness et al, 2015; Kwon and Han, 2018; Bannwarth et al, 2019). METH abuse has been shown to result in cognitive deficits in attention, learning, and memory in a variety of experimental and clinical studies (Potvin et al, 2018; Seyedhosseini Tamijani et al, 2018). Several dose regimens of METH administration have been evaluated in different studies, such as a single high dose (40 mg/kg) or repeated (4 × 10 mg/kg, 2–3-h intervals) or escalating (1–10 mg/kg, twice a day, at 5-h intervals, for 10 days) doses of METH and chronic voluntary oral METH intake (Yang et al, 2018).…”

Mechanism of psychoactive substance-induced cognitive disorders: does tau protein play a role?

“…Besides, a 12-week aerobic exercise may have beneficial effects on METH dependent patients with verbal learning and memory deficits [78]. In animal studies, chronic METH treatment could also impair cognitive functions [79][80][81][82][83], including deficits in reversal learning [79], disorders in alert exploratory behavior [80], impairments in recognition memory [81] and so on. In addition, Seyedhosseini et al [82] pointed out that repeated METH administration impaired only long-term recognition memory in somehow dose dependent manner while short-term remained unchanged.…”