Central cannabinoid receptors modulate acquisition of eyeblink conditioning

Abstract

Delay eyeblink conditioning is established by paired presentations of a conditioned stimulus (CS) such as a tone or light, and an unconditioned stimulus (US) that elicits the blink reflex. Conditioned stimulus information is projected from the basilar pontine nuclei to the cerebellar interpositus nucleus and cortex. The cerebellar cortex, particularly the molecular layer, contains a high density of cannabinoid receptors (CB1R). The CB1Rs are located on the axon terminals of parallel fibers, stellate cells, and basket cells where they inhibit neurotransmitter release. The present study examined the effects of a CB1R agonist WIN55,212-2 and antagonist SR141716A on the acquisition of delay eyeblink conditioning in rats. Rats were given subcutaneous administration of 1, 2, or 3 mg/kg of WIN55,212-2 or 1, 3, or 5 mg/kg of SR141716A before each day of acquisition training (10 sessions). Dose-dependent impairments in acquisition were found for WIN55,212-2 and SR141716A, with no effects on spontaneous or nonassociative blinking. However, the magnitude of impairment was greater for WIN55,212-2 than SR141716A. Dose-dependent impairments in conditioned blink response (CR) amplitude and timing were found with WIN55,212-2 but not with SR141716A. The findings support the hypothesis that CB1Rs in the cerebellar cortex play an important role in plasticity mechanisms underlying eyeblink conditioning.

Figure 1.

Mean ± SE conditioned response percentage for rats given 1 mg/kg (white square), 2 mg/kg (black triangle), or 3 mg/kg (white circle) of WIN55,212-2 or vehicle (black diamond) during spontaneous blinks (sp), unpaired (up), and acquisition (P1–P10) sessions.

Figure 2.

Mean ± SE conditioned response amplitude for rats given 1 mg/kg (white square), 2 mg/kg (black triangle), or 3 mg/kg (white circle) of WIN55,212-2 or vehicle (black diamond) during paired CS–US sessions.

Figure 3.

Mean ± SE conditioned response onset latency for rats given 1 mg/kg (white square), 2 mg/kg (black triangle), or 3 mg/kg (white circle) of WIN55,212-2 or vehicle (black diamond) during paired CS–US sessions.

Figure 4.

Mean ± SE conditioned response percentage for rats given 1 mg/kg (white square), 3 mg/kg (black triangle), or 5 mg/kg (white circle) of SR141716A or vehicle (black diamond) during spontaneous blinks (sp), unpaired (up), and acquisition (P1–P10) sessions.

Figure 5.

Mean ± SE conditioned response amplitude for rats given 1 mg/kg (white square), 3 mg/kg (black triangle), or 5 mg/kg (white circle) of SR141716A or vehicle (black diamond) during paired CS–US sessions.

Figure 6.

Mean ± SE conditioned response onset latency for rats given 1 mg/kg (white square), 3 mg/kg (black triangle), or 5 mg/kg (white circle) of SR141716A or vehicle (black diamond) during paired CS–US sessions.