Chronic amphetamine treatment affects collicular-dependent behaviour

Abstract

Distractibility can be defined as an attention deficit where orientation toward irrelevant targets cannot be inhibited. There is now mounting evidence that the superior colliculus is a key neural correlate of distractibility, with increased collicular-activity resulting in heightened distractibility. Heightened distractibility is reduced by amphetamine, which acutely suppresses collicular responsiveness. However, when amphetamine is used to treat distractibility, it is given chronically, yet no data exist on whether chronic amphetamine treatment affects the colliculus. Here, the effect of chronic amphetamine treatment was assessed in healthy hooded lister rats on two collicular dependent behaviours following a twenty-eight day treatment period: i) orienting to visual stimuli, and ii) height-dependent modulation of air-righting. We found no significant impact of amphetamine treatment on visual orienting despite showing dose-dependent decreases in orienting to repeated stimuli. However, we did find that treatment with amphetamine significantly reduced the ability to modulate righting according to the height the animal is dropped from - a function known to be dependent on the colliculus. We suggest that the results are in line with previous research showing acute amphetamine suppresses collicular activity and we speculate that the psychostimulant may increase receptive field size, altering time-to-impact calculations carried out by the colliculus during air-righting.

Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal

“…This has been found previously for other brain regions following chronic treatment with amphetamine, albeit given intraperitoneally (Peterson et al, 2006). This suppression would be consistent with our behavioural effects previously reported which suggest that chronic amphetamine treatment reduces activity in the colliculus and suppresses collicular dependent behaviour (Turner et al, 2018a).…”

“…For example, acute amphetamine has been shown to suppress activity in the visually responsive superficial layers of the SC in healthy animals (Dommett et al, 2009;Gowan et al, 2008) and in rodent models of ADHD (Clements et al, 2014). In addition, we have recently demonstrated that chronic treatment with orally-administered amphetamine selectively alters colliculardependent behaviour in a manner consistent with suppression of activity in the area (Turner et al, 2018a). Furthermore, amphetamine is known to act on dopaminergic neurons to increase synaptic dopamine levels, and based on previous research (Rolland et al, 2013) we can infer that this should suppress visual responses in the colliculus.…”

“…All treatment took place in the holding room, after daily weighing of the rats (to determine dose and monitor health status), at the start of the dark phase. Three doses of amphetamine were selected (10 mg/kg, 5 mg/kg, and 2 mg/Kg) to ensure some clinical relevance and included those that have previously been shown to impact on collicular-dependent behaviours (Turner et al, 2018a). The final day of treatment fell on a Friday and in all cases subsequent procedures were conducted between 3 and 14 days after treatment end are summarised in Figure 1.…”