Short- and Long-Term Cognitive Effects of Chronic Cannabinoids Administration in Late-Adolescence Rats

Abstract

The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. treatment with the CB1/CB2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg) for two weeks during the late adolescence period (post-natal days 45–60) and tested for behavioral and electrophysiological measures of cognitive performance 24 hrs, 10 and 30 days after the last drug injection. The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP) in the ventral subiculum (vSub)-nucleus accumbens (NAc) pathway were temporary as they lasted only 24 h or 10 d after withdrawal. However, chronic WIN significantly impaired hippocampal dependent short-term memory measured in the object location task 24 hrs, 10, 30, and 75 days after the last drug injection. Our findings suggest that some forms of hippocampal-dependent short-term memory are sensitive to chronic cannabinoid administration but other cognitive impairments are temporary and probably result from a residue of cannabinoids in the brain or acute withdrawal effects from cannabinoids. Understanding the effects of cannabinoids on cognitive function may provide us with tools to overcome these impairments and for cannabinoids to be more favorably considered for clinical use.

Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood

“…No such difference was found in the ES + veh (t (7) ¼ 0.370, NS) group suggesting poor performance. The NoES + WIN group also demonstrated poor performance (t (7) ¼ 2.170, P ¼ 0.067), corroborating with a previous study from our laboratory (Abush and Akirav 2012). No significant differences in total exploration time were found in males in the sample (F (3,32) ¼ 1.013, NS) or test (F (3,32) ¼ 1.14, NS) phase.…”

“…See Abush and Akirav (2012). Two identical objects (10 × 8 × 7 cm) were located in the openfield, under dim light, 10 cm from the walls.…”

“…Previous studies have suggested the time window from P28 to P42 as a prototypic period during which rats of most breeding stocks exhibit adolescent-typical characteristics, although this does not imply that older and younger animals cannot be considered as adolescents (for review, see Schneider 2013;Spear 2000). We use the term "adolescence" for the time window P28-45 and the term "late adolescence" for P45-60 (Abush and Akirav 2012).…”

“…We have shown that 2 wk administration of the CB1/2 receptor agonist WIN55,212-2 (WIN) during late adolescence (postnatal day (P)45-60) impaired hippocampal dependent short-term memory measured in the object location task even 75 d after the last drug injection (Abush and Akirav 2012). However, there were no long-term effects on other memory tasks (Morris water maze, novel object recognition) and plasticity.…”

Cannabinoid Receptor Activation Prevents the Effects of Chronic Mild Stress on Emotional Learning and LTP in a Rat Model of Depression

“…Potentiation was measured as a percentage of change from the average of the 30 min baseline before HFS (Abush and Akirav, 2013). The amplitude was measured by peak-to-peak values based on the previous findings of LTP in the vSub-NAc pathway (Abush and Akirav, 2012;Dong et al, 2007). However, it is the slope that is considered to reflect LTP (ie, the strengthening of existing synaptic contacts), whereas the amplitude may also reflect the activity of the cells (Abush and Akirav, 2013).…”