3. Umbruch 4.4..2005 - Online Pot

Cannabinoids in appetite and obesity 225
antagonist SR-141716 was confirmed by using CB 1 receptor-knockout mice.
While SR-141716 significantly reduced food intake in wild-type mice, it was
totally ineffective in mice lacking the CB 1 receptor [35, 47]. Moreover, it was
shown that following temporary food restriction, the knockout mice eat less
than their wild-type littermates. These results suggest the existence of an
endogenous cannabinoid orexigenic tone which, when disrupted, may lead to
decreased food consumption.
Interaction between cannabinoids and hormones controlling energy
homeostasis
The link between cannabinoids and the anorexigenic hormone leptin was first
suggested by Di Marzo et al. in 2001 [35]. Acute leptin treatment of normal
mice and ob/ob mice (mutant mice lacking the leptin gene) not only decreased
food intake but also resulted in decreased levels of anandamide and 2-AG in
the hypothalamus. On the other hand, defective leptin signaling was associated
with elevated hypothalamic but not cerebellar levels of endocannabinoids in
obese db/db and ob/ob mice and Zucker rats [35]. These findings suggest a
direct link between endogenous cannabinoids and the leptin-controlled energy
homeostasis. Moreover, interactions between the cannabinoid system and
other neuropeptides involved in the control of food intake have also been suggested
in the literature. A cross-talk between the orexin-1 and the CB 1 receptors
was recently described [48], and a synergistic interaction between CB 1
and melanocortin MC4 systems in feeding behavior has also been reported
[49]. Moreover, the co-expression of hypothalamic CB 1 mRNA with corticotropin-releasing
hormone (CRH), cocaine-amphetamine-regulated transcript
(CART) and melanin-concentrating hormone (MCH) may also be indicative of
possible interactions between the cannabinoid system and these peptides.
Cannabinoids and motivational processes
Ingestive behaviors, however, are not only linked to energy homeostasis control,
as the brain-reward system, a complex neural network activated by pleasurable
stimuli also mediates the incentive or hedonic value of food. The association
of the cannabinoid system with the motivational processes is indicated
by several lines of evidence. The preference for palatable sweet-food intake
induced by administration of cannabinoid agonists in both humans and laboratory
animals is most likely indicative of the involvement of an effect on the
brain-reward systems. Moreover, the CB 1 antagonist SR-141716 not only
selectively decreased the intake of sweet or palatable food, but also decreased
both alcohol [29, 32] and nicotine self-administration in rats [50]. It also
decreased heroin self-administration in rats [51] and was shown to reduce the
reinforcing value of the median forebrain bundle (MFB) electrical stimulation