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. 2023 Jan 12;24(2):1477. doi: 10.3390/ijms24021477

Table 2.

Noradrenergic modulation of spike-wave discharges and similar phenomena.

Model Type of Treatment Target Effect Reference
Tottering mice 6-OHDA (s.c., dose 100 mg/kg)
Acute effect on the first or second day after birth
Noradrenergic terminals (hyperinnervation)
+
Noradrenergic terminals (destruction)
Decrease in total duration of SWDs Noebels, 1984 [72]
GAERS rats Salbutamol (i.p., 1.25–50, acute)
Isoprenaline (i.p., 12.5–100, acute)
Beta AR (activation) No effect Micheletti et al., 1987 [40]
Propranolol (i.p., 1.25–80, acute) Beta AR (inhibition) No effect
Prazosin (i.p., 0.25–4, acute) Alpha1 AR (inhibition) Increase in SWDs total duration
ST 587 (i.p., 1–4, acute)
Cirazoline (i.p., 0.1–4, acute)
Alpha1 AR (activation) Decrease in SWDs total duration
Clonidine (i.p., 0.01–0.1, acute) Alpha2 AR (activation) Increase in SWDs total duration
Yohimbine (i.p., 0.5–8, acute) Alpha2 AR (inhibition) <2 mg/kg: decrease in SWD total duration
>4 mg/kg: very short decrease in SWDs total duration followed by the disappearance of the effect
Desipramine (i.p., 5–40, acute) NA reuptake (inhibition)
5HT reuptake (inhibition)
No effect
Mianserine (i.p., 1.25–40, acute) NA release (activation)
alpha1 AR (inhibition)
alpha2 AR (inhibition)
5HT receptors (inhibition)
No effect
Fischer 344 rats 6-OHDA (i.c., 200 μg, two injections with 48 h interval) Noradrenergic terminals (destruction) Increase in HVS incidence (4–7 days after administration) Buzsáki et al., 1991 [41]
6-OHDA (i.th., 50 μg, one injection) Increase in HVS incidence (4–7 days after administration)
DSP-4 (i.p., 50 mg/kg, acute) No effect (4–7 days after administration)
+
Xylazine (i.th., acute)
Increase in HVS incidence after intracisternal or intrathalamic 6-OHDA
Clonidine (i.p., 0.02 or 0.1 mg/kg) Alpha2 AR (activation) Increase in HVS incidence
Xylazine (i.p., 0.5 or 2 mg/kg) Alpha2 AR (activation) Increase in HVS incidence
Yohimbine (i.p., 1 or 5 mg/kg, acute) Alpha2 AR (inhibition) Decrease in HVS incidence
1 mg/kg: maximal effect
Prazosin (i.p., 0.5 or 2 mg/kg) Alpha1 AR (inhibition) Increase in HVS incidence
Desipramine (i.p., 1 or 10 mg/kg, acute)
Amitriptyline (i.p., 1 or 10 mg/kg, acute)
NA reuptake (inhibition)
5HT reuptake (inhibition)
Decrease in HVS incidence
Amitriptyline (i.p., 10 mg/kg, 21 days) NA reuptake (inhibition)
5HT reuptake (inhibition)
alpha2 AR (decreased density)
Decrease in HVS incidence
Decrease of the effect of intrathalamic xylazine
Decrease of the effect of IP xylazine—not significant
Clonidine (i.th., bilateral, 0.1 or 1 nmol, acute) Alpha2 AR (activation) Increase in HVS incidence (suppressed by 5 nmol of yohimbine)
Clonidine (i.th., unilateral, 10 or 100 pmol, acute) Alpha2 AR (activation) Increase in HVS amplitude
WAG/Rij rats Clonidine (i.p., 0.00625 mg/kg, acute) Alpha2 AR (activation) Increase in SWDs incidence
Decrease in total EEG power in the frontal cortex
Increase in total EEG power in RTN
Decrease in intracortical coherence
Sitnikova and Luijtelaar 2005 [42]
Dexmedetomidine (i.p., 1 mg/kg, IP, acute) Alpha2 AR (activation) Decrease in total SWDs number (very high dose) Al-Gailani et al., 2022 [73]
GAERS rats Atipamezole (i.c.v., 1–31 µg, acute) Alpha2 AR (inhibition) 12/31 µg: decrease in SWDs incidence and SWDs mean duration Yavuz et al., 2020 [43]
Atipamezole (i.c.v., 12 µg, 5 days) Alpha2 AR (inhibition) Decrease in total SWDs duration
Dexmedetomidine (i.c.v., 0.1, 0.5, 2.5 µg, acute) Alpha2 AR(activation) Increased in total SWD, absence status epilepticus Yavuz et al., 2022 [74]
Charles River rats Clonidine (p.o., 0.0001–0.1 mg/kg, acute) Alpha2 AR (activation) Increase in the mean duration of SWDs Kleinlogel, 1985 [75]
Guanfacine (p.o., 0.0001–0.1 mg/kg, acute) Alpha2 AR (activation) Increase in the mean duration of SWDs
Yohimbine (p.o., 0.1–10 mg/kg, acute) Alpha2 AR (inhibition) Decrease in the mean duration of SWDs (maximal effect with dose 1 mg/kg).
3.2 mg/kg: suppressed the effect of guanfacine (1 mg/kg)
Prazosin (p.o., 0.32–10 mg/kg, acute) Alpha1 AR (inhibition) Increase in the mean duration of SWD
Long-Evans rats Yohimbine (i.p., 0.5–10 mg/kg, acute) Alpha2 AR (inhibition) 0.5–5 mg/kg: decrease in the mean duration of FEAD
10 mg/kg: no effect
King and Burnham, 1982 [76]
Wistar rats Atipamezole (s.c., 0.1/1/10 mg/kg, acute) Alpha2 AR (inhibition) 0.1 mg/kg: no effect
1/10 mg/kg: suppression of HVS
Riekkinen et al., 1990 [77]
Guanfacine (i.p., 0.004/0.02/0.1 mg/kg, acute) Alpha2 AR (activation) Increase in HVS incidence and duration (0.004 mg/kg: no effect on duration)
+
Atipamezole (1 mg/kg): suppressed an increase in HVS duration
Atipamezole (10 mg/kg): suppressed an increase in HVS duration and incidence
+
unilateral RT lesion (VB also damaged)
No HVS on the contralateral side; HVS still occurred on the ipsilateral side
Atipamezole (s.c., minipump, 0.1 mg/kg/h, continuous) Alpha2 AR (inhibition) Decrease in HVS incidence during the 6-day administration
No changes in sensitivity to Guanfacine (i.p., 0.001 mg/kg, acute)
Jäkälä et al., 1992 [78]
Aged Wistar rats (10–12 months) Atipamezole (i.p., 0.01–4 mg/kg, acute) Alpha2 AR (inhibition) Decrease in HVS incidence Yavich et al., 1994 [79]
Idazoxan (i.p., 0.1–4 mg/kg, acute) Alpha2 AR (inhibition) <0.5 mg/kg: decrease in HVS incidence
>0.5 mg/g: disappearance of the effect
Yohimbine (i.p., 0.1–4 mg/kg, acute) Alpha2 AR (inhibition) <0.5 mg/kg: decrease in HVS incidence
>0.5 mg/g: disappearance of the effect
Dexmedetomidine (i.p., 0.005 mg/kg, acute) Alpha2 AR(activation) Increase in HVS incidence
Prazosin (i.p., 1 mg/kg, acute) Alpha1 AR (inhibition) Increase in HVS incidence

Abbreviations: AR—adrenoreceptor, NA—noradrelaine, 5HT—serotonin. Type of EEG activity: FEAD—flash-evoked after discharge, HVS—high voltage spindles (the waveform similar to spike-wave discharges), SWDs—spike-wave discharges. Type of administration: i.p.,—intraperitoneal, i.c.—intracisternal; i.th.—intrathalamic; i.c.v.—intracerebroventricular, PO—perioral, SC—subcutaneous.