Neuroscience 2003 Abstract
| Presentation Number: | 904.6 |
|---|---|
| Abstract Title: | Functional tolerance and blockade of long-term depression at excitatory synapses in the nucleus accumbens following repeated cannabinoid administration. |
| Authors: |
Hoffman, A. F.*1
; Oz, M.1
; Caulder, T.1
; Lupica, C. R.1
1DHHS, NIH, NIDA Intramural Res. Program, Cell. NeuroBiol. Br., Cell. Neurophys. Section, Baltimore, MD |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Synaptic Plasticity -- Long-term depression (LTD) |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Addiction and Drugs of Abuse<br />-- Opioids and others |
| Session: |
904. LTD/LTP Pharmacology Poster |
| Presentation Time: | Wednesday, November 12, 2003 2:00 PM-3:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # D55 |
| Keywords: | DRUG ABUSE, SYNAPTIC PLASTICITY, BRAIN SLICE, ELECTROPHYSIOLOGY |
The effects of marijuana on brain reward pathways, including the nucleus accumbens (NAc), may contribute to its addictive potential. Within the NAc, both the acute presynaptic inhibitory effects of cannabinoids, and the role of endogenous cannabinoids in the establishment of long-term depression (LTD) at glutamatergic synapses, have been described. However, changes in synaptic function following repeated cannabinoid exposure have not been investigated. Electrophysiological recordings were performed in rat brain slices prepared 24h following a 7 day treatment with a vehicle solution, delta-9-tetrahydrocannabinol (Δ9-THC, 10 mg/kg), or the cannabinoid agonist WIN55,212-2 (10 mg/kg). Glutamatergic postsynaptic potentials in the NAc were inhibited by WIN55,212-2 in slices from vehicle-treated animals (EC50 = 143 nM). Concentration-response curves were significantly shifted to the right in slices obtained from both chronic WIN55,212-2-treated animals (EC50 = 1.2 μM), and from rats chronically treated with Δ9-THC(EC50 = 1.2 μM). The inhibition of GABAergic inhibitory postsynaptic currents by WIN55,212-2 was also significantly reduced in slices from chronically treated rats. Repeated electrical stimulation (10 Hz, 5min) of glutamatergic afferents to the NAc resulted in LTD that was blocked by the CB1 receptor antagonist SR141716A, confirming earlier reports of its dependence on endogenous cannabinoids. However, LTD was not observed in slices from rats chronically treated with Δ9-THC or WIN55,212-2. These data reveal that repeated cannabinoid exposure reduces the acute inhibitory effects of cannabinoids at NAc synapses, and blocks endocannabinoid-dependent LTD in the NAc. These changes may reflect neurobiological adaptations that occur in brain reward pathways following prolonged marijuana use.
Supported by NIDA-IRP
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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