The nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. Therefore, it is necessary to understand the actions of abused drugs such as marijuana ands its derivatives on physiology of this system. The NAc medium spiny GABAergic neurons (MSNs) receive innervation from other intrinsic MSNs, and glutamatergic innervation from extrinsic sources. Both GABAergic and glutamatergic synapses onto MSNs are inhibited by drugs of abuse, suggesting that this action may contribute to the rewarding properties of these drugs. To investigate the actions of cannabinoids (CBs) in the NAc, we performed whole-cell recordings from MSNs in rat brain slices. Accomplishments attributable to this project in the past year include the establishment of a chronic delta-9-tetrahydrocannabinol (THC) treatment paradigm that successfully resulted in tolerance to various pharmacological effects of THC. This tolerance was also noted in the diminished inhibition of field excitatory postsynaptic potentials (EPSPs)in the nucleus accumbens shell. These studies are currently continuing by measuring synaptic EPSPs in single cells, determining whether withdrawal can be precipitated through antagonist application, and whether this withdrawal can be observed at the synaptic level. Additional experiments to be performed this year will examine wheter endogenous cannabinoids can alter synaptic physiology in the nucleus accumbens, and whether these endogenously released cannabinoids can alter long-term synaptic plasticity in this brain structure.
| Lupica, Carl R; Riegel, Arthur C (2005) Endocannabinoid release from midbrain dopamine neurons: a potential substrate for cannabinoid receptor antagonist treatment of addiction. Neuropharmacology 48:1105-16 |
| Lupica, Carl R; Riegel, Arthur C; Hoffman, Alexander F (2004) Marijuana and cannabinoid regulation of brain reward circuits. Br J Pharmacol 143:227-34 |
| Hoffman, Alexander F; Oz, Murat; Caulder, Tara et al. (2003) Functional tolerance and blockade of long-term depression at synapses in the nucleus accumbens after chronic cannabinoid exposure. J Neurosci 23:4815-20 |
| Gerdeman, Gregory L; Partridge, John G; Lupica, Carl R et al. (2003) It could be habit forming: drugs of abuse and striatal synaptic plasticity. Trends Neurosci 26:184-92 |
