Naturalistic operant responses in deer mice (Peromyscus maniculatus bairdii) and its response to outcome manipulation and serotonergic intervention

Abstract

Investigating the motivational triggers underlying naturalistic compulsive-like behavior is generally regarded as challenging. To this extent, the current study aimed to establish a proof-of-concept for future investigation by probing unconditioned and naturalistic operant responses aimed at obtaining nesting material by normal (NNB) and large (LNB) nest building deer mice (Peromyscus maniculatus bairdii). LNB mice and NNB controls were individually placed in cages equipped with a lever-operated nesting material (cotton rope) dispenser and allowed to become accustomed to the response (lever press)-outcome (obtaining cotton rope) contingency over seven nights. Subsequently, the contingency was manipulated by withdrawing the nesting material (experiment 1) or punishing the lever-press response with a mild electrical foot shock (experiment 2). Mice were then treated for 28 days with escitalopram (50 mg/kg/d) and retested. Our results indicate that (1) LNB mice generally made more operant responses compared to NNB controls, (2) withdrawal of nesting material and institution of punishment bolstered responding in LNB but not NNB mice and (3) escitalopram treatment tended to reduce increased responding in LNB mice following experimental manipulation, while normalizing the total number of lever-press counts in the LNB cohort. Therefore, LNB seems to diverge from NNB, not only as a spontaneous phenotype, but also in terms of the motivation to obtain nesting material, despite demotivating feedback. That such differences were abrogated by chronic escitalopram intervention, indicates that the uniquely motivated operant interactions displayed by LNB mice, may be founded upon serotonergic mechanisms, a finding in line with the neurobiological theory of obsessive-compulsive disorder.

Behavioral restriction, lorazepam, and escitalopram uniquely influence the expression of naturalistic stereotypy in deer mice: perspectives on anxiety- and compulsive-like behavior

“…Escitalopram oxalate [ESC; BLD Pharma ® , Shanghai, China; 50 mg/kg/day; Wolmarans et al ( 2013 )] and LOR [Aspen Pharmacare ® , Qheberha, South Africa; 2 mg/kg/day; Wolmarans et al ( 2022 )] were prepared for sub-acute (8-day) and chronic (35-day) oral administration via the drinking water, respectively. These concentrations were based on the average daily liquid consumption of deer mice [0.25 ml/g/day; Wolmarans et al ( 2013 ) and de Brouwer et al ( 2020 )]. Drug intake was confirmed by means of daily liquid consumption measurements (average liquid intake of mice receiving normal water, escitalopram, and lorazepam was similar across all days of testing; mixed-effects analysis; inter-day effect: F (29,500) = 1.18, p = 0.24; between-exposure effect: F (2,23) = 1.78, p = 0.19; Kruskal-Wallis analysis of the average liquid intake over time per exposure group: p = 0.37; average liquid consumption over all days of testing: 4.1 ml per animal; average escitalopram consumption per day: 0.82 ± 0.2 mg; average lorazepam consumption per day: 0.033 ± 0.008 mg).…”

Stereotypy and spontaneous alternation in deer mice and its response to anti‐adenosinergic intervention

“…Importantly, deer mice drink fluid at an average rate of 0.25 ml/g/24 hr (de Brouwer, Fick, et al., 2020). Although this has not been shown to change as a function of drug exposure or additives added to the drinking water (de Brouwer, Fick, et al., 2020; de Brouwer, Harvey, et al., 2020), the average daily fluid intake per cage was monitored by weighing the residual amount of liquid left on each following day (Supplementary Information). Istradefylline was constituted in concentrations that ensured the delivery of the appropriate doses to animals over a 24‐hr period (4 and 8 mg/100 ml for the 10 and 20 mg kg −1 day −1 doses, respectively).…”

Associations between nesting, stereotypy, and working memory in deer mice: response to levetiracetam

“…10,386:2021). The number of animals included in this investigation was broadly based on extensive prior investigation where we showed that at least 30-45% of mice develop LNB [34,[36][37][38][39] and motor stereotypies [40][41][42][43] in adulthood.…”