Exercise-induced endocannabinoid signaling is modulated by intensity.

Endocannabinoids (eCB) are endogenous ligands for cannabinoid receptors that are densely expressed in brain networks responsible for reward. Recent work shows that exercise activates the eCB system in humans and other mammals, suggesting eCBs are partly responsible for the reported improvements in mood and affect following aerobic exercise in humans. However, exercise-induced psychological changes reported by runners are known to be dependent on exercise intensity, suggesting that any underlying molecular mechanism should also change with varying levels of exercise intensity.

Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high'.

Humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the 'runner's high', which may function to encourage habitual aerobic exercise. Endocannabinoids (eCBs) are endogenous neurotransmitters that appear to play a major role in generating these rewards by activating cannabinoid receptors in brain reward regions during and after exercise. Other species also regularly engage in endurance exercise (cursorial mammals), and as humans share many morphological traits with these taxa, it is possible that exercise-induced eCB signaling motivates habitual high-intensity locomotor behaviors in cursorial mammals.

Differential response to a selective cannabinoid receptor antagonist (SR141716: rimonabant) in female mice from lines selectively bred for high voluntary wheel-running behaviour.

Exercise is a naturally rewarding behaviour in human beings and can be associated with feelings of euphoria and analgesia. The endocannabinoid system may play a role in the perception of neurobiological rewards during and after prolonged exercise. Mice from lines that have been selectively bred for high voluntary wheel running (high runner or HR lines) may have evolved neurobiological mechanisms that increase the incentive salience of endurance-type exercise.

Context-specific reversal of cocaine sensitization by the CB1 cannabinoid receptor antagonist rimonabant.

The CB(1) cannabinoid receptor is implicated in the rewarding properties of many drugs of abuse, including cocaine. While CB(1) receptor involvement in the acute rewarding properties of cocaine is controversial, CB(1) antagonists such as SR141716 (rimonabant) have clearly been found to prevent cue- and cocaine-elicited reinstatement of cocaine self-administration in rodents. Here we demonstrate the novel involvement of CB(1) receptors in the maintenance of behavioral sensitization to cocaine in C57BL/6 mice.

Disruption of endocannabinoid release and striatal long-term depression by postsynaptic blockade of endocannabinoid membrane transport.

Activation of the CB1 cannabinoid receptor inhibits neurotransmission at numerous synapses in the brain. Indeed, CB1 is essential for certain types of both short- and long-term synaptic depression. It was demonstrated recently that CB1 is critical for activity-dependent long-term depression (LTD) at glutamatergic corticostriatal synapses in acute brain slice preparations.

It could be habit forming: drugs of abuse and striatal synaptic plasticity.

Drug addiction can take control of the brain and behavior, activating behavioral patterns that are directed excessively and compulsively toward drug usage. Such patterns often involve the development of repetitive and nearly automatic behaviors that we call habits. The striatum, a subcortical brain region important for proper motor function as well as for the formation of behavioral habits, is a major target for drugs of abuse.