Anxiety conditioned to nicotine in the elevated plus-maze is time dependent

Abstract

Conditioning to the anxiogenic effects of nicotine has previously been demonstrated in the social interaction test and there was no generalization of conditioning between the social interaction and elevated plus-maze tests. Because the two tests generate distinct states of anxiety, the conditioning could have occurred to the cues associated with the test environment and/or to those associated with the type of anxiety generated by the test. The elevated plus-maze permits separation of these two factors, because quite distinct states of anxiety are generated on trials 1 and 2, whereas the apparatus cues remain the same. Rats that had been tested on day 1 in the plus-maze, 5 min after nicotine (0.45 mg/kg), showed a conditioned anxiogenic response when tested undrugged on day 2. This was shown by significantly lower percentages of open-arm entries and percentage of time spent on the open arms, compared with control groups. Thus, conditioning to apparatus cues is sufficient to mediate a conditioned anxiogenic effect. The importance of the timing of the nicotine-associated cues was demonstrated by the failure to obtain conditioned anxiogenic effects when rats were exposed to the plus-maze on day 1, 30 min after nicotine (0.45 or 0.1 mg/kg).

Nicotine and cannabinoids: Parallels, contrasts and interactions

“…For example, the phenomenon of test-specific conditioned anxiety to an anxiogenic dose of nicotine has been demonstrated in both the social interaction and the elevated plus-maze tests (File et al, 2002a;Tucci et al, 2002). The corticotrophin releasing factor antagonist, a-helical CRF 9-41 reversed this conditioned anxiety, but not nicotine-induced unconditioned anxiety, providing evidence that conditioned anxiety is mediated by a different mechanism from unconditioned anxiety (Tucci et al, 2003a).…”

Timing of conditioned responding in a nicotine locomotor conditioning preparation: manipulations of the temporal arrangement between context cues and drug administration

“…These nicotine-conditioned associations can be studied using various preclinical models [10,18,33,43]. Recently, our laboratory has employed a locomotor conditioning task with rats ( [5,7,30,31]; see also [13,32,44]).…”

Chronic Nicotine Treatment Leads to Induction of Tyrosine Hydroxylase in Locus Ceruleus Neurons: The Role of Transcriptional Activation

“…A single immobilization leads to a rapid, but transient stimulation of TH gene transcription rate; repeated immobilization is associated with a sustained transcriptional response (Osterhout et al, 1997;Serova et al, 1999b). Furthermore, File and coworkers (Irvine et al, 1999;Tucci et al, 2002) have shown that at high doses chronic nicotine treatment is anxiogenic and consequently stressful. Hence, we have tested whether a sustained transcriptional response is observed in the LC, as well as the adrenal after repeated immobilization stress.…”