Examining the effects of former cannabis use on cerebellum-dependent eyeblink conditioning in humans

TY - JOUR

T1 - Examining the effects of former cannabis use on cerebellum-dependent eyeblink conditioning in humans

AU - Steinmetz, Adam B.

AU - Edwards, Chad R.

AU - Vollmer, Jennifer M.

AU - Erickson, Molly A.

AU - O'Donnell, Brian F.

AU - Hetrick, William P.

AU - Skosnik, Patrick D.

N1 - Funding Information: Acknowledgements This work was supported in part by grants from NIDA 1 R21 DA023097-01A1 (PDS) and NARSAD (PDS). The authors wish to thank Peter Finn, Giri Krishnan, Jennifer Vohs, Ken Mackie, and the late Michael Walker for their input and help throughout the project.

PY - 2012/5

Y1 - 2012/5

N2 - Rationale: Previous work in humans has shown that chronic cannabis users exhibit disruptions in classical eyeblink conditioning (EBC), a form of associative learning that is known to be dependent on the cerebellum. Based upon previous work in animals, it was hypothesized that these learning deficits were related to cannabinoid receptor (CB1R) downregulation. However, it remains unclear whether there is a recovery of cerebellum-dependent learning after the cessation of cannabis use. Methods: Therefore, former cannabis users (n=10), current cannabis users (n=10), and cannabis-naïve controls (n=10), all free of DSM-IV Axis-I or -II disorders, were evaluated. A standard delay EBC procedure was utilized in which paired presentations of a conditioned stimulus (CS; e.g., tone) and a co-terminating unconditioned stimulus (US; e.g., ocular airpuff) were administered, thus eliciting a conditioned eyeblink response (CR). The primary dependent measures were percentage of CRs and CR latency across conditioning blocks. Results: Similar to prior studies, current cannabis users exhibited marked impairments in both the acquisition and timing of CRs compared to controls. Although former cannabis users showed intact CR acquisition compared to controls, they exhibited significantly impaired (shorter) CR latencies. In both cannabis groups, UR amplitude did not differ from controls, indicating normal US processing. Conclusions: These data suggest that a recovery of function has occurred for the learning of the CS-US association, while the accurate timing of the CR shows lasting impairments. Taken together, these results suggest that heavy cannabis use can disrupt timing-related synaptic plasticity within the cerebellum, even after the cessation of cannabis use.

AB - Rationale: Previous work in humans has shown that chronic cannabis users exhibit disruptions in classical eyeblink conditioning (EBC), a form of associative learning that is known to be dependent on the cerebellum. Based upon previous work in animals, it was hypothesized that these learning deficits were related to cannabinoid receptor (CB1R) downregulation. However, it remains unclear whether there is a recovery of cerebellum-dependent learning after the cessation of cannabis use. Methods: Therefore, former cannabis users (n=10), current cannabis users (n=10), and cannabis-naïve controls (n=10), all free of DSM-IV Axis-I or -II disorders, were evaluated. A standard delay EBC procedure was utilized in which paired presentations of a conditioned stimulus (CS; e.g., tone) and a co-terminating unconditioned stimulus (US; e.g., ocular airpuff) were administered, thus eliciting a conditioned eyeblink response (CR). The primary dependent measures were percentage of CRs and CR latency across conditioning blocks. Results: Similar to prior studies, current cannabis users exhibited marked impairments in both the acquisition and timing of CRs compared to controls. Although former cannabis users showed intact CR acquisition compared to controls, they exhibited significantly impaired (shorter) CR latencies. In both cannabis groups, UR amplitude did not differ from controls, indicating normal US processing. Conclusions: These data suggest that a recovery of function has occurred for the learning of the CS-US association, while the accurate timing of the CR shows lasting impairments. Taken together, these results suggest that heavy cannabis use can disrupt timing-related synaptic plasticity within the cerebellum, even after the cessation of cannabis use.

KW - Abstinence

KW - Cannabinoids

KW - Cerebellum

KW - Conditioning

KW - Drug abuse

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U2 - https://doi.org/10.1007/s00213-011-2556-1

DO - https://doi.org/10.1007/s00213-011-2556-1

M3 - Article

C2 - 22134474

SN - 0033-3158

VL - 221

SP - 133

EP - 141

JO - Psychopharmacologia

JF - Psychopharmacologia

IS - 1

ER -