Repeated stimulation of L-type calcium channels in the rat ventral tegmental area mimics the initiation of behavioral sensitization to cocaine.
BACKGROUND
A substantial body of evidence indicates that ion flux through L-type calcium channels and N-methyl-D-aspartate (NMDA) receptors contributes to behavioral sensitization to cocaine.


OBJECTIVE
The following experiments were designed to evaluate the role of calcium influx through L-type calcium channels or NMDA receptors in the ventral tegmental area (VTA) in the initiation of behavioral sensitization to cocaine.


METHODS
The L-type calcium channel agonist BayK 8644, the glutamate agonist NMDA, or vehicle was microinjected into the VTA on 3 consecutive days. Following a 2-week withdrawal period, all rats received a challenge injection of cocaine (15 mg/kg, i.p.) in order to assess potential cross-sensitization with the NMDA or BayK 8644 pretreatments.


RESULTS
Repeated intra-VTA microinjections of BayK 8644, but not NMDA, resulted in an augmentation of the behavioral response to cocaine.


CONCLUSIONS
These results indicate that calcium influx through L-type calcium channels produces neurophysiological adaptations that mimic those resulting from intermittent exposure to cocaine.
Licata
S C
SC
Department of Pharmacology, Boston University School of Medicine, MA 02118, USA.
Freeman
A Y
AY
Pierce-Bancroft
A F
AF
Pierce
R C
RC
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D013239:Stereotyped Behavior / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000502:physiology*
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D018765:Dopamine Uptake Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D003042:Cocaine