NeuropharmacologyAmygdalar vasopressin mRNA increases in acute cocaine withdrawal: Evidence for opioid receptor modulation
Section snippets
Experimental procedures
Male Fischer rats (190–220g, Charles River Laboratories, Kingston, NY, USA) were housed individually in a stress-minimized facility with free access to food and water. Animals were adapted to a standard 12-h light/dark cycle (lights on from 10:30 h to 22:30 h) for 7 days, and then received i.p. injections of cocaine (3×15mg/kg) or equal volumes of saline for 14 days in their home cages following the “binge” pattern regimen: three times daily at 1 h intervals (11:00, 12:00 and 13:00 h) (Branch
Amygdala
In the chronic cocaine experiment, neither chronic “binge” cocaine administration nor naloxone challenge altered AVP mRNA levels (Fig. 1). In the cocaine withdrawal experiment, two-way ANOVA showed a significant Cocaine×Naloxone interaction (F(1,27)=5.49, P<0.05) (Fig. 1). Acute withdrawal led to a significant increase in AVP mRNA levels (Newman-Keuls post hoc test, P<0.05). When the rats were treated with naloxone during acute withdrawal, the AVP mRNA increase was significantly attenuated (P
Discussion
We found that AVP mRNA levels in the amygdala were not altered after chronic “binge” cocaine. However, acute cocaine withdrawal was associated with increased amygdalar AVP mRNA levels, nearly three-fold that of the control level (Fig. 1). Also, this effect occurred at acute withdrawal stage (3 h), persisted for 1 day into subacute cocaine withdrawal, but not for 10 days of chronic withdrawal (Fig. 3). This novel finding parallels our recent studies demonstrating an increased AVP mRNA level in
Conclusion
The present studies determined the effects of chronic “binge” cocaine and its acute withdrawal on stress responsive AVP gene expression. We found that acute cocaine withdrawal resulted in a significant increase in amygdalar AVP mRNA levels. Of interest, amygdalar AVP gene expression stimulated by acute cocaine withdrawal was completely blocked by a single, moderate dose of naloxone, indicating an opioid receptor activation-mediated mechanism. In line with this finding, we have recently found an
Acknowledgments
The authors would like to thank Dr. G. Aguilera for providing the V1b receptor cDNAs; Dr. G. Uhl for the MOP-r cDNA; Dr. J. Roberts for the POMC cDNA; and Drs. T. Nilsen and P. Maroney for the 18S DNA. The work was supported by NIDA Research Center Grant DA-P60-05130 and DA-00049 (M.J.K.), and by NIH Training Grant GM07524 (J.T.B.).
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