*Co esponding au ho : Venka eshwa a Rao Joginapally
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion Liscense 4.0.
Neu obeha io al E ec s o High-Suga Die Assessed Using In elliCage: Impai men s
in Lea ning, Memo y, Cogni i e Flexibili y and Addic ion-like Beha io in Mice
Wajaha h Mohammed Siddiqui, Nagilla Bhaske and Venka eshwa a Rao Joginapally *
Depa men o Zoology, Uni e si y College o Science, Osmania Uni e si y, Hyde abad. Telangana, India. 500 007.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 24(01), 186-192
Publica ion his o y: Recei ed on 04 Sep embe 2025; e ised on 07 Oc obe 2025; accep ed on 10 Oc obe 2025
A icle DOI: h ps://doi.o g/10.30574/wjbphs.2025.24.1.0896
Abs ac
Excessi e consump ion o die a y suga has been linked o me abolic and neu ocogni i e dys unc ion, ye he beha io al
consequences emain insu icien ly cha ac e ized. Using he In elliCage au oma ed beha io al sys em, we in es iga ed
he long- e m impac o a high-suga die (HSD) on lea ning, memo y, cogni i e lexibili y, ac i i y, and addic ion-like
beha io s in mice. Adul swiss albino mice we e di ided in o con ol (s anda d chow) and HSD g oups o 6 weeks.
Beha io al asks included place lea ning, e e sal lea ning, ac i i y moni o ing, and suc ose p e e ence. Mice on HSD
exhibi ed de ici s in acquisi ion and e en ion o memo y asks, impai ed e e sal lea ning indica i e o educed
cogni i e lexibili y, al e ed locomo o ac i i y, and enhanced suga p e e ence esembling addic ion-like beha io .
These indings sugges ha ch onic HSD consump ion impai s cogni i e pe o mance in mice, wi h implica ions o
unde s anding die - ela ed neu ocogni i e diso de s in humans.
Keywo ds: High-suga die ; In elliCage; Memo y; Cogni i e lexibili y; Addic ion-like beha io ; Mice
1. In oduc ion
The global inc ease in suga consump ion has aised conce ns abou i s po en ial impac on heal h, no only in e ms o
obesi y and me abolic synd ome bu also ega ding cogni i e and beha io al ou comes [1,2]. Epidemiological s udies
sugges links be ween excessi e suga in ake and cogni i e decline, pa icula ly in hippocampus-dependen memo y
[3]. Animal models ha e shown ha high-suga die s can impai lea ning, memo y, and synap ic plas ici y [4–6].
T adi ional beha io al assays o oden s o en in ol e human in e e ence, which may in oduce bias and s ess. The
In elliCage sys em p o ides an au oma ed, high- h oughpu , and e hologically ele an pla o m o beha io al
assessmen in g oup-housed mice [7]. This sys em allows con inuous moni o ing o ac i i y, lea ning, and p e e ence
beha io s unde minimally in asi e condi ions.
The p esen s udy aimed o e alua e he e ec s o ch onic high-suga die consump ion on neu obeha io al unc ions
in mice, ocusing on memo y, ac i i y, cogni i e lexibili y, and addic ion-like beha io s using In elliCage pa adigms.
2. Ma e ials and Me hods
2.1. Animals and Housing
Adul male swiss albino mice (n=4, 8 weeks old) we e housed in g oups unde s anda d 12:12 h ligh -da k cycles. All
expe imen al p ocedu es we e app o ed by he Ins i u ional Animal E hics Commi ee.
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2.2. Die s
Con ol g oup (G oup-1) (n=2): s anda d oden chow and wa e ad libi um. High-suga die (HSD) g oup (G oup-2)
(n=2): chow supplemen ed wi h 25% suc ose solu ion as d inking wa e . The die a y egimen las ed 6 weeks.
2.3. In elliCage Sys em
The In elliCage (TSE Sys ems, Ge many) consis s o ou ope an condi ioning co ne s equipped wi h RFID de ec o s,
doo s, and lick senso s. Mice we e iden i ied ia RFID mic ochips.
2.4. Beha io al P o ocols
• Adap a ion Phase: all co ne s accessible, ee explo a ion.
• Place Lea ning Task: mice lea ned o associa e one co ne wi h wa e access.
• Re e sal Lea ning (Cogni i e Flexibili y): co ec co ne shi ed a e acquisi ion.
• Ac i i y Moni o ing: spon aneous isi s and nose-pokes eco ded.
• Suc ose P e e ence Tes (Addic ion-like beha io ): p e e ence o suc ose s wa e moni o ed.
2.5. Da a Analysis
Beha io al pa ame e s (lea ning cu es, e o a es, co ne isi s, lick coun s) we e ex ac ed using In elliCage
so wa e. G oup compa isons we e pe o med using - es s, wi h signi icance se a p = 0.05 (Fig. 1C).
3. Resul s
3.1. Gene al Ac i i y
HSD mice displayed dec eased nosepokes and co ne isi s and educed explo a o y a iabili y, sugges ing lesse
ac i i y wi h es ic ed pa e ns (Fig. 1A, 1B, 1C).
Figu e 1A G aph ep esen ing he numbe o nosepokes in con ol(G oup-1) s. high-suga die (HSD) mice(G oup-2)
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Figu e 1B Table showing he numbe o co ne isi s in con ol(G oup-1) s. high-suga die (HSD) mice(G oup-2)
Figu e 1C S a is ical analysis ( -Tes )
Figu e 1 Gene al Ac i i y Pa e ns
3.2. Lea ning and Memo y
Du ing place lea ning, con ol mice quickly acqui ed he co ec co ne (co ne -2), while HSD mice equi ed
signi ican ly mo e ials and made mo e e o s o acqui ing he co ec co ne (co ne -3) (Fig. 2A, 2B, 2C). Re en ion
es s con i med impai ed memo y consolida ion in HSD mice.
Figu e 2 Lea ning and Cogni i e Flexibili y
Figu e 2A Lea ning and e o cu es o con ol(G oup-1) and HSD(G oup-2) mice du ing place lea ning
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Figu e 2B E o a es o con ol(G oup-1) and HSD(G oup-2) mice du ing place lea ning
Figu e 2C Co ec co ne p e e ence o con ol(G oup-1, co ne -2) and HSD(G oup-2, co ne -3) mice du ing place
lea ning
3.3. Cogni i e Flexibili y
In e e sal lea ning, con ol mice adap ed o new condi ions wi hin a day, whe eas HSD mice exhibi ed p olonged
pe se e a ion and signi ican ly delayed adap a ion (Fig. 2D, 2E).
Figu e 2D E o a es o con ol(G oup-1) and HSD(G oup-2) mice du ing e e sal lea ning.
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Figu e 2E Co ec co ne p e e ence o con ol(G oup-1, co ne -3) and HSD(G oup-2, co ne -2) mice du ing e e sal
lea ning
3.4. Addic ion-like Beha io
Suc ose p e e ence was signi ican ly highe in HSD mice, wi h compulsi e co ne checking as sugges ed by hei
beha iou owa ds no mal wa e as suc ose was una ailable (Fig. 3).
Figu e 3 Numbe o licks and du a ion o con ac ime o con ol(G oup-1) and HSD(G oup-2) mice
Figu e 3 Addic ion-like Beha io
Table 1 Summa y o Beha io al Ou comes
Beha io al
Domain
Measu e
Con ol G +oup
HSD G oup
Gene al Ac i i y
Co ne isi s, Nosepokes
Mo e
Fewe
Lea ning &
Memo y
Co ec co ne p e e ence,
E o s
Mo e co ec co ne
p e e ence, Fewe e o s
Less co ec co ne
p e e ence, Mo e e o s
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Cogni i e
Flexibili y
Re e sal lea ning
adap a ion
Wi hin a day
Delayed
Addic ion-like
Beha io
Lick numbe , Du a ion o
con ac ime
Fewe lick numbe , Mo e
con ac ime
Highe lick numbe , Less
con ac ime
4. Discussion
Ou indings demons a e ha ch onic high-suga die impai s lea ning, memo y, and cogni i e lexibili y in mice while
enhancing addic ion-like p e e ence beha io s. These esul s align wi h p e ious oden s udies showing die -induced
hippocampal dys unc ion and dopamine signaling al e a ions [8–10].
The In elliCage sys em allowed con inuous, au oma ed assessmen , educing expe imen e bias and s ess- ela ed
a i ac s. Impo an ly, he obse ed beha io al impai men s mi o ea ly cogni i e symp oms in humans wi h excessi e
suga consump ion and me abolic dys unc ion [11,12].
Mechanis ically, suga -induced insulin esis ance, hippocampal synap ic plas ici y educ ion, and al e ed dopamine
ansmission may unde lie hese e ec s [13,14]. Fu u e s udies should in eg a e neu ophysiological and molecula
analyses, as well as es po en ial in e en ions such as closed-loop neu omodula ion, o mi iga e suga -induced
cogni i e decline.
Limi a ions: This s udy used only male mice, and e ec s in emales may di e . Addi ionally, molecula co ela es we e
no examined.
5. Conclusion
Ch onic high-suga die leads o educed ac i i y, impai ed memo y, educed cogni i e lexibili y, and addic ion-like
beha io in mice. These esul s highligh he cogni i e isks o mode n die a y pa e ns and suppo u he
ansla ional esea ch.
Compliance wi h e hical s anda ds
Disclosu e o con lic o in e es
No con lic o in e es wi h any esea h g oup.
Re e ences
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