Neuroscience 2003 Abstract
| Presentation Number: | 462.6 |
|---|---|
| Abstract Title: | Cannabinoid CB1 receptors inhibit GABA-B mediated synaptic currents in midbrain dopamine neurons. |
| Authors: |
Riegel, A. C.*1
; Williams, J. T.2
; Lupica, C. R.1
1Cell. Neurophysiol. Unit, NIDA-IRP, NIH/DHHS, Baltimore, MD 2OR, 5500 Nathan Shock Dr, 21224, |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Neurotransmitters -- Cannabinoids |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Synaptic Transmission<br />-- Presynaptic mechanisms |
| Session: |
462. Cannabinoids I Poster |
| Presentation Time: | Monday, November 10, 2003 2:00 PM-3:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # C22 |
| Keywords: | VENTRAL TEGMENTAL AREA, SYNAPTIC TRANSMISSION, ELECTROPHYSIOLOGY, DRUG ABUSE |
Evidence suggests a role in the brain for receptors activated by synthetic cannabinoids (CBs), Δ9-THC, and endogenous agonists known as endocannabinoids. The best characterized physiological role for CB receptors in brain is the presynaptic inhibition of GABA release from axon terminals providing input to GABA-A receptors throughout the CNS. This phenomenon has been observed with the synthetic CB agonist WIN55,212-2 in brain slices containing the ventral tegmental area (VTA), a brain region thought to be essential to the rewarding properties of many commonly abused drugs. Whereas the activation of GABA-A receptors in the VTA is thought to reflect the activity of axon terminals derived from intrinsic neurons, inputs to GABA-B receptors on dopamine (DA) neurons in the VTA are likely derived from GABAergic neurons located in forebrain regions such as the nucleus accumbens. To determine whether cannabinoids could regulate GABAergic input to GABA-B receptors on DA neurons, we performed whole-cell voltage clamp recordings aided by DIC-IR microscopy in living rat brain slices. GABA-B receptor-mediated inhibitory postsynaptic currents (IPSCs) were elicited in VTA DA neurons with trains of electrical stimuli (50 Hz;5 pulses), and pharmacologically isolated from other synaptic currents. These currents were blocked by the GABA-B antagonist CGP35348. The synthetic CB agonist WIN55,212 reduced peak GABA-B IPSC amplitudes in a concentration-dependent fashion (max = -43.8±5.3%, EC50 = 365 nM), and this effect was completely blocked by the selective CB1 cannabinoid receptor antagonist AM-251. In addition, AM-251, alone, did not alter GABA-B IPSCs in these VTA DA neurons under baseline conditions. These data suggest that CB1 receptors can regulate GABA release onto DA neurons in the VTA, possibly altering cellular firing patterns, thereby contributing to the rewarding effects of marijuana.
Supported by NIDA-IRP, NIH
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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