Does long term potentiation in periacqueductal gray (PAG) mediate lasting changes in rodent anxiety-like behavior (ALB) produced by predator stress?--Effects of low frequency stimulation (LFS) of PAG on place preference and changes in ALB produced by predator stress

Abstract

The effects on rodent behavior of low frequency bilateral stimulation (LFS, 900 pulses at 1 Hz) of periacqueducatal gray (PAG) was investigated. The first experiment examined aversive qualities of LFS in a place preference paradigm. There was no evidence of a place preference after 1 or 7 applications of LFS. After the first LFS, rats showed longer latencies to leave the conditioned chamber, suggesting a positively reinforcing effect of LFS. Latency differences were not accounted for by freezing or immobility prior to leaving. Rats with electrodes outside the PAG did not show these effects. After repeated LFS, stimulated rats did not differ from controls in place preference or in anxiety-like behavior (ALB). Experiment 2 studied the effects of predator stress in unimplanted rats on an extended battery of measures of ALB in hole board, plus maze and light/dark box tests of rodent anxiety. Effects of electrode damage in the PAG on ALB was also examined. In addition, the effect of 7 applications of bilateral LFS of PAG on ALB following a 5 min unprotected exposure of rats to a cat (predator stress) was examined. Predator stress lastingly changed a wide variety of behaviors in the plus maze, [Rodgers, Behav. Pharmacol. 8 (1997) 477] replicating and extending previous reports. A new finding is an increase in light avoidance in the light/dark box test. Moreover, factor analysis revealed open arm avoidance, risk assessment, light avoidance and cautious exploration loaded on independent factors, replicating and extending previous findings. Bilateral, but not unilateral, damage specific to PAG was also found to be anxiolytic in plus maze measures of ALB. Bilateral implants in the PAG seemed to prevent many of the effects of predator stress on ALB measured 8 days later. Nevertheless, predator stress did decrease head dips in the open arm and LFS reversed this effect. Light avoidance also increased following predator stress and LFS reversed this increase. These findings suggest the PAG occupies an important position in the final common path of substrate changes mediating effects of predator stress on a range of behaviors in the rodent. The fact that LFS in the PAG can reverse stress induced changes in behavior supports the idea that LTP in PAG mediates stress induced increases in anxiety in rodents, as it does in the cat [Adamec, Neurosci. Biobevav. Rev. 21(6) (1997) 755; Adamec, J. Psychopharmacol. 2000 (in press); Adamec, J. Psychopharmacol. 2000 (in press); Adamec, J. Psychopharmacol. 12(2) (1998) 129; Adamec, J. Psychopharmacol. 12(13) (1998) 227].