Effects on Development 645cognitive development, and behavior showed that the consequences of prenatal
exposure to marijuana are subtle. Before the age of 3 years, there is little evidence
for a prenatal effect either upon growth or behavior. However, beyond this age,
there are several findings suggestive of an association between prenatal marijuana
exposure and aspects of frontal lobe functioning, including cognitive behavior.
Attention/impulsivity and problem-solving situations requiring integration and
manipulation of basic visuo-perceptual skills appear to be particularly affected
(Fried and Smith 2001).
These results were replicated in a longitudinal cohort study conducted in Pitts-
burgh to investigate the consequences of prenatal marijuana in offspring beyond
early school age. Prenatal marijuana exposure was also found to affect attention
and impulsivity, and, thereby, to decrease the ability to plan and execute tasks
(Leech et al. 1999). These data are in agreement with the results obtained in an-
imals. In these models, it has been reported that deficits of cognitive functions
induced by marijuana use during adulthood could be mainly attributable to the
activation of CB 1 receptors located in the hippocampus, a brain region crucial for
certain forms of learning and memory. Prenatal exposure to a cannabinoid ago-
nist produced memory deficits linked to dysfunction in hippocampal long-term
potentiation and glutamate release (Mereu et al. 2003).
2
Ontogeny of the Endogenous Cannabinoid System
The existence of several components of the endogenous cannabinoid system has
been demonstrated in the fetal and neonatal rat brain. The system is active in this
period of life and shows significant differences in the expression and/or activity of
its components during the consecutive steps of early stages of development.
Most of the studies carried out on the presence and/or the activity of the com-
ponents of this system during development have focused on the cannabinoid CB 1
receptor (Mailleux and Vanderhaeghen 1992a; Romero et al. 1997; Berrendero et
al. 1998; Buckley et al. 1998; Mato et al. 2003). There is also some information about
the cannabinoid receptor ligands anandamide (AEA) and 2-arachidonoylglycerol
(2-AG) (Berrendero et al. 1999).
2.1
Cannabinoid Receptors
Cannabinoid CB 1 receptor binding and mRNA levels could be detected around ges-
tational day (GD)11–14 in rats, coinciding with the time of phenotypic expression
of most of the neurotransmitters (for review see Insel 1995). At these fetal ages,
cannabinoid receptors appear to be functional, since they are already coupled to
signal transduction mechanisms that involve activation of guanosine triphosphate
(GTP)-binding proteins (Berrendero et al. 1998). Pharmacological activation of
cannabinoid receptors during the developmental period has been associated with