Anticonvulsive Effects and Pharmacokinetic Profile of Cannabidiol (CBD) in the Pentylenetetrazol (PTZ) or N-Methyl-D-Aspartate (NMDA) Models of Seizures in Infantile Rats

In spite of use of cannabidiol (CBD), a non-psychoactive cannabinoid, in pediatric patients with epilepsy, preclinical studies on its effects in immature animals are very limited. In the present study we investigated anti-seizure activity of CBD (10 and 60 mg/kg administered intraperitoneally) in two models of chemically induced seizures in infantile (12-days old) rats. Seizures were induced either with pentylenetetrazol (PTZ) or N-methyl-D-aspartate (NMDA). In parallel, brain and plasma levels of CBD and possible motor adverse effects were assessed in the righting reflex and the bar holding tests. CBD was ineffective against NMDA-induced seizures, but in a dose 60 mg/kg abolished the tonic phase of PTZ-induced generalized seizures. Plasma and brain levels of CBD were determined up to 24 h after administration. Peak CBD levels in the brain (996 ± 128 and 5689 ± 150 ng/g after the 10- and 60-mg/kg doses, respectively) were reached 1–2 h after administration and were still detectable 24 h later (120 ± 12 and 904 ± 63 ng/g, respectively). None of the doses negatively affected motor performance within 1 h after administration, but CBD in both doses blocked improvement in the bar holding test with repeated exposure to this task. Taken together, anti-seizure activity of CBD in infantile animals is dose and model dependent, and at therapeutic doses CBD does not cause motor impairment. The potential risk of CBD for motor learning seen in repeated motor tests has to be further examined.     

Rising verbal intelligence scores: Implications for research and clinical practice.

Evidence suggests that scores on various intelligence tests have been rising at a fast rate. To find out whether performance on the Wechsler Adult Intelligence Scale (WAIS) Vocabulary subtest has also been rising, the authors searched major psychology journals for investigations involving healthy younger and older adult participants and collected the reported WAIS Vocabulary scores. The meta-analysis shows that WAIS Vocabulary scores have been rising at the rate of 0.117/year (corresponding to 1.52 IQ points/decade) for younger adults and 0.367/year (corresponding to 4.79 IQ points/decade) for older adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Episodic spatial memory in adulthood.

Two experiments examined age-related differences in memory for spatial location information in a museum exhibit (Exp 1) and in a secretarial office (Exp 2). In Exp 1, Ss were the visitors to the exhibit (N?=?302, 15–74 yrs of age), and memory was assessed using a map test. In Exp 2, Ss were 64 young adults (M?=?21.2 yrs) and 32 older adults (M?=?71.2 yrs), and memory was assessed using both a map test and a relocation test. The relocation test required Ss to replace the to-be-remembered targets where they appeared at study. Exp 1 showed an age-related decline in spatial memory performance, and it placed the onset of this decline in the 6th decade of life. Exp 2 showed an age-related decline on both tests, but age effects were smaller on the relocation test than on the map test, and when Ss knew that spatial memory would be tested than when they were not informed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Self-report measures of prospective memory are reliable but not valid.

Are self-report measures of prospective memory (ProM) reliable and valid? To examine this question, 240 undergraduate student volunteers completed several widely used self-report measures of ProM including the Prospective Memory Questionnaire (PMQ), the Prospective and Retrospective Memory Questionnaire (PRMQ), the Comprehensive Assessment of Prospective Memory (CAPM) questionnaire, self-reports of retrospective memory (RetM), objective measures of ProM and RetM, and measures of involvement in activities and events, memory strategies and aids use, personality and verbal intelligence. The results showed that both convergent and divergent validity of ProM self-reports are poor, even though we assessed ProM using a newly developed, reliable continuous measure. Further analyses showed that a substantial proportion of variability in ProM self-report scores was due to verbal intelligence, personality (conscientiousness, neuroticism), activities and event involvement (busyness), and use of memory strategies and aids. ProM self-reports have adequate reliability, but poor validity and should not be interpreted as reflecting ProM ability. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Object orientation information in semantic and episodic memory.

Investigated the contributions of object orientation information in semantic and episodic memories to implicit and explicit memory test performance, in 3 experiments. 456 undergraduates were shown color photos of objects, and their memory was assessed either with an old/new recognition test or with a test that required Ss to identify slowly faded objects. The critical variables were the type of photo and the orientation at which the photos were displayed. Half of the targets were displayed in study condition and the rest in non-study condition (baseline). Results show that in Exp 1, baseline identification was slower for objects displayed upside down rather than upright. Baseline orientation-specific effects were much larger for cardinal than non-cardinal objects in Exps 2 and 3. The extent to which orientation is coded in the semantic and episodic memory representations of different kinds of objects is discussed. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adenosine Kinase Isoforms in the Developing Rat Hippocampus after LiCl/Pilocarpine Status Epilepticus

LiCl/pilocarpine status epilepticus (SE) induced in immature rats leads, after a latent period, to hippocampal hyperexcitability. The excitability may be influenced by adenosine, which exhibits anticonvulsant activity. The concentration of adenosine is regulated by adenosine kinase (ADK) present in two isoforms—ADK-L and ADK-S. The main goal of the study is to elucidate the changes in ADK isoform expression after LiCl/pilocarpine SE and whether potential changes, as well as inhibition of ADK by 5-iodotubercidin (5-ITU), may contribute to changes in hippocampal excitability during brain development. LiCl/pilocarpine SE was elicited in 12-day-old rats. Hippocampal excitability in immature rats was studied by the model of hippocampal afterdischarges (ADs), in which we demonstrated the potential inhibitory effect of 5-ITU. ADs demonstrated significantly decreased hippocampal excitability 3 days after SE induction, whereas significant hyperexcitability after 20 days compared to controls was shown. 5-ITU administration showed its inhibitory effect on the ADs in 32-day-old SE rats compared to SE rats without 5-ITU. Moreover, both ADK isoforms were examined in the immature rat hippocampus. The ADK-L isoform demonstrated significantly decreased expression in 12-day-old SE rats compared to the appropriate naïve rats, whereas increased ADK-S isoform expression was revealed. A decreasing ADK-L/-S ratio showed the declining dominance of ADK-L isoform during early brain development. LiCl/pilocarpine SE increased the excitability of the hippocampus 20 days after SE induction. The ADK inhibitor 5-ITU exhibited anticonvulsant activity at the same age. Age-related differences in hippocampal excitability after SE might correspond to the development of ADK isoform levels in the hippocampus.