Voluntary Exercise and Sucrose Consumption Enhance Cannabinoid CB1 Receptor Sensitivity in the Striatum

Abstract

The endogenous cannabinoid system is involved in the regulation of the central reward pathway. Running wheel and sucrose consumption have rewarding and reinforcing properties in rodents, and share many neurochemical and behavioral characteristics with drug addiction. In this study, we investigated whether running wheel or sucrose consumption altered the sensitivity of striatal synapses to the activation of cannabinoid CB1 receptors. We found that cannabinoid CB1 receptor-mediated presynaptic control of striatal inhibitory postsynaptic currents was remarkably potentiated after these environmental manipulations. In contrast, the sensitivity of glutamate synapses to CB1 receptor stimulation was unaltered, as well as that of GABA synapses to the stimulation of presynaptic GABAB receptors. The sensitization of cannabinoid CB1 receptor-mediated responses was slowly reversible after the discontinuation of running wheel or sucrose consumption, and was also detectable following the mobilization of endocannabinoids by metabotropic glutamate receptor 5 stimulation. Finally, we found that the upregulation of cannabinoid transmission induced by wheel running or sucrose had a crucial role in the protective effects of these environmental manipulations against the motor and synaptic consequences of stress.

Biphasic Effects of Cannabinoids in Anxiety Responses: CB1 and GABAB Receptors in the Balance of GABAergic and Glutamatergic Neurotransmission

“…Therefore, the conditions established were predominantly similar to the basal activity of these mice, promoting a less aversive environment for the animals as possible. In agreement with these observations, stressful stimuli, as well as rewarding experiences, were reported to mediate changes in the expression level of the CB1 receptor specifically in GABAergic terminals (Rossi et al, 2008;De Chiara et al, 2010). Interestingly, the stress-mediated regulation of the GABAergic CB1 receptor was postulated as a compensatory mechanism required to restore the equilibrium between GABAergic and glutamatergic neurotransmission in emotional homeostasis (Ruehle et al, 2012).…”

Brain-Derived Neurotrophic Factor Controls Cannabinoid CB1 Receptor Function in the Striatum

“…To study the effects of natural rewards, a group of mice (n ϭ 30) were housed in a cage equipped with a running wheel for 15 d. Another group of mice (n ϭ 30) was reared in control cages, but they were allowed to consume ad libitum a drinking fluid containing sucrose (3% in tap water) for 7 d. Both 15 d running wheel and 7 d sucrose consumption have already been reported to enhance the sensitivity of CB 1 Rs (GABA) to the CB 1 receptor agonist HU210 [(6aR,10aR)-3-(1,1Ј-dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6 H-dibenzo[b,d] Chiara et al, 2010). At the end of these environmental manipulations, mice from both rewarded groups (n ϭ 8 per group) were killed along with control animals of the same age (n ϭ 8) to measure BDNF levels in the striatum and in the hippocampus.…”

“…d] cyclohepten-5,10-imine maleate] (30 M) and CNQX (10 M) were added to the external solution to block, respectively, NMDA and non-NMDA glutamate receptors. Tetrodotoxin (TTX) (1 M) was also continuously applied to study mIPSCs (Centonze et al, 2007;De Chiara et al, 2010). For kinetic analysis, events with peak amplitude between 10 and 50 pA were grouped, aligned by half-rise time, normalized by peak amplitude, and averaged to obtain rise times, decay times, and half-widths.…”

“…Whole-cell patch-clamp recordings from single striatal neurons in corticostriatal coronal slices (200 m) were performed as described previously De Chiara et al, 2010). To detect spontaneous (sIPSCs) or miniature (mIPSCs) GABA A -mediated IPSCs, intraelectrode solution had the following composition (in mM): 110 CsCl, 30 K ϩ -gluconate, 1.1 EGTA, 10 HEPES, 0.1 CaCl 2 , 4 Mg-ATP, and 0.3 Na-GTP.…”

“…Intrastriatal infusion of BDNF, in fact, elicits a depressive behavior (Eisch et al, 2003), as also does a stress protocol causing the downregulation of striatal CB 1 Rs (Berton et al, 2006;Rossi et al, 2008). Furthermore, the anxiousdepressive behavior induced by social stress is abolished by either blockade of BDNF signaling in this brain area (Berton et al, 2006) or sensitization of CB 1 Rs regulating striatal GABA synapses (De Chiara et al, 2010). These data argue against a synergistic action of CB 1 Rs and BDNF and rather suggest that BDNF contrasts the activity of CB 1 Rs.…”