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B 0.25 hr 24 hr 1 week 2 weeks uurrem (ua) Tjme p0St-Treatmem

Hgurc 6. Following the establishment of stable baseline responding (less than 10% between-days variability) rats received acute administration of hll.-2 (Lfljig).The cytokine disrupted responding for rewarding stimulation from the lateral hypothalamus in a current titration paradigm. Relative to baseline, responding was reduced at the intermediate and higher cuirent intensities, and this effect was evident as long as 1 week following cytokine treatment (left-hand panel). The current threshold necessary to provoke half-maximal responding was increased commensurately (right-hand pane!) (from An ism an et al., 1<MK).

crimination component). Under these conditions a single administration of 1L-2 (LOpg; 2.4 x lO3 units from R&D Systems) provoked modest, but statistically significant reductions of responding for rewarding brain stimulation (Anisman, Kokkinidis, & Merali, 1996; Anisman, Kokkinidis, Borowski, & Merali, 1998) (see Figure 6), Interestingly, this effect was still evident 24-168hr afterward. As in the case of stressor effects, if animals received the cytokine, but were not tested until some time afterward (e.g. 7 days), then responding for rewarding brain stimulation was unimpaired. In effect, in order for long-term deficits to be evident, it was necessary for animals to experience the stimulation in the presence of the cytokine effects (possibly reflecting either an extinction-like response due to lack of reward, or a conditioned suppression like that seen when responding is aversive ). In contrast to the effects of the cytokine on responding for rewarding brain stimulation, discrimination performance was unaffected by the treatment. That is, rats continued to emit the response to the + stimulus and not to the—stimulus. Coupled with the data indicating that acute IL-2 treatment did not affect exploration, or spontaneous alternation, these data suggest that animals were capable of appropriately attending to environmental stimuli, and maintaining a learned response. Thus, these data are consistent with the view that IL-2 may promote anhe-donic effects.

As in our studies with rats, it was observed that icv IL-2 administration in CD-I mice (5.0ng) impaired responding for rewarding stimulation from the dorsal aspect of the ventral tegmentum (Hebb,Zacharko,& Anisman, 1998).The VTA contains the cell bodies of the mesocorticolimbic system, and is thought to be fundamental in subserving rewarding brain stimulation. As the dorsal and ventral aspects of the VTA are differentially influenced by stressors (Zacharko & Anisman, 1991), we assessed the impact of icv IL-2 on responding for rewarding stimulation from both these regions. It was observed that in a titration paradigm (in this experiment frequency rather than current intensity was altered in order to minimize current spread) IL-2 impaired responding from the dorsal VTA. Although there were few animals with electrodes located in the ventral aspcct of the VTA, it appeared that IL-2 did not disrupt responding from this

Easei-ne 0.25 Hr 24 hr

2 weeks

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Brain Blaster

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