Intracerebellar cannabinoid administration impairs delay but not trace eyeblink conditioning

Abstract

Intracerebellar administration of cannabinoid agonists impairs cerebellum-dependent delay eyeblink conditioning (EBC) in rats. It is not known whether the cannabinoid-induced impairment in EBC is found with shorter interstimulus intervals (ISI), longer ISIs, or with trace EBC. Moreover, systemic administration of cannabinoid agonists does not impair trace EBC, suggesting that cannabinoid receptors within the cerebellum are not involved in trace EBC. To more precisely assess the effects of cannabinoids on cerebellar learning mechanisms the current study examined the effects of the cannabinoid agonist WIN55,212-2 (WIN) infusion into the area of the cerebellar cortex necessary for EBC (the eyeblink microzone) in rats during short delay (250 ms CS), long delay (750 ms CS), and trace (250 ms CS, 500 ms trace interval) EBC. WIN was infused into the eyeblink microzone 30 min before pretraining sessions and five EBC training sessions, followed by five EBC training sessions without infusions to assess recovery from drug effects and savings. WIN had no effect on spontaneous blinks or non-associative responses to the CS or US during the pretraining sessions. Short and long delay EBC were impaired by WIN but trace EBC was unaffected. The results indicate that trace EBC is mediated by mechanisms that are resistant to cannabinoid agonists.

The mouse at the popcorn stage of development

“…The jumping behaviour observed after cocaine (Areal et al, 2015) or quinpirole (Luque‐Rojas et al, 2013) interacted with the endocannabinoid system (Zou et al, 2019), implying its possible influence on popcorn jumping. Peripherally administered cannabinoid receptor agonists caused cerebellar‐type dysfunctions in motor coordination (Patel & Hillard, 2001) and intra‐cerebellar injections of these agents mimicked cerebellar lesions in pavlovian conditioning (Steinmetz & Freeman, 2020). Dopamine may also interact with glutamate in view of the excessive jumping reported in Glt1 mice deficient in the astrocytic glutamate transporter (Jia et al, 2021) and with histamine in view of the excessive jumping reported in Hdc mice deficient in histamine (Abdurakhmanova et al, 2019), both mentioned above, or else with GABA in view of popcorn‐like jumping in mice injected with high dose levels of the GABA A receptor agonist, alfaxalone (Siriarchavatana et al, 2016).…”

Differential Effects of Two Early Life Stress Paradigms on Cerebellar-Dependent Delay Eyeblink Conditioning

“…Relatedly, cannabinoid receptor type 1 (CB1R) knockout mice exhibit poor dEBC acquisition and retention of the conditioned response 36 . In a series of studies, Steinmetz and Freeman have shown that CB1R agonists injected peripherally or infused into cerebellar cortex prior to dEBC impair conditioning [37][38][39][40][41] . CB1R agonists facilitate dEBC if administered one hour after dEBC sessions 40 .…”

Stimulatory effect of monoacylglycerol lipase inhibitor MJN110 on locomotion and step kinematics demonstrated by high-precision 3D motion capture in mice

“…The high expression of cannabinoid receptors in cerebellum and basal ganglia [30][31][32] suggests that careful assessment of subtle motor effects of cannabinoid receptor activation will be necessary. Presently the research on effects of cannabinoids on precise movement in rodents is, however, limited [33][34][35][36][37] but cannabinoids have been shown to have effects on eyeblink [38] and kinematics of gait in humans [39].…”