The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats - PubMed (original) (raw)

The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats

S Erb et al. J Neurosci. 1998.

Abstract

We have shown previously that footshock stress and priming injections of cocaine reinstate cocaine seeking in rats after prolonged drug-free periods (Erb et al., 1996). Here we examined the role of brain corticotropin-releasing factor (CRF) and the adrenal hormone corticosterone in stress- and cocaine-induced reinstatement of cocaine seeking in rats. The ability of footshock stress and priming injections of cocaine to induce relapse to cocaine seeking was studied after intracerebroventricular infusions of the CRF receptor antagonist D-Phe CRF12-41, after adrenalectomy, and after adrenalectomy with corticosterone replacement. Rats were allowed to self-administer cocaine (1.0 mg/kg/infusion, i.v) for 3 hr daily for 10-14 d and were then placed on an extinction schedule during which saline was substituted for cocaine. Tests for reinstatement were given after intermittent footshock (10 min; 0.5 mA) and after priming injections of saline and cocaine (20 mg/kg, i.p.). Footshock reinstated cocaine seeking in both intact animals and animals with corticosterone replacement but not in adrenalectomized animals. The CRF receptor antagonist D-Phe CRF12-41 blocked footshock-induced reinstatement at all doses tested in both intact animals and animals with corticosterone replacement. Reinstatement by priming injections of cocaine was only minimally attenuated by adrenalectomy and by pretreatment with D-Phe CRF12-41. These data suggest that brain CRF plays a critical role in stress-induced, but only a modulatory role in cocaine-induced, reinstatement of cocaine seeking. Furthermore, the data show that although reinstatement of cocaine seeking by footshock stress requires minimal, basal, levels of corticosterone, stress-induced increases in corticosterone do not play a role in this effect.

PubMed Disclaimer

Figures

Fig. 1.

Top, The effect of the CRF receptor antagonist

-Phe CRF12–41(

-Phe) on the mean ± SEM total number of responses (saline infusions + time-out responses) on the active lever in 3 hr tests for reinstatement after_Saline_ (physiological saline, 1.0 ml/kg, i.p.; 5 min before the start of the session), Footshock(intermittent footshock, 10 min; 0.5 mA; 0.5 sec on; mean off period of 40 sec; immediately before the start of the session), and_Cocaine_ (20 mg/kg, i.p.; 5 min before the start of the session). Groups of intact animals were tested in each reinstatement test condition under one dose of

-Phe given intracerebroventricularly (0 μg, n = 10; 0.1 μg, n = 9; 0.3 μg, n = 11; and 1.0 μg, n = 10). The _asterisk_indicates a difference from the 0 μg dose of

-Phe in the same test condition; Mann–Whitney (p < 0.05).Bottom, The effect of

-Phe on the mean number of responses (saline infusions + time-out responses) on the active lever in each hour of each of the 3 hr tests for reinstatement. The_asterisk_ indicates a difference from all doses of

-Phe in the_Footshock_ test condition in hour 1; Mann–Whitney (p < 0.05).

Fig. 2.

Top, The effect of adrenalectomy (ADX; n = 11) and corticosterone replacement (CORT/PW; n = 9) and sham surgery (SHAM;n = 10) on the mean ± SEM total number of responses (saline infusions + time-out responses) on the active lever in 3 hr tests for reinstatement after Saline(physiological saline, 1.0 ml/kg, i.p.; 5 min before the start of the session), Footshock (intermittent footshock, 10 min; 0.5 mA; 0.5 sec on; mean off period of 40 sec; immediately before the start of the session), and Cocaine (20 mg/kg, i.p.; 5 min before the start of the session). Animals in each group (SHAM, ADX, and CORT/PW) were tested under all three test conditions. The_asterisk_ indicates a difference from SHAM and CORT/PW in the Footshock test condition; Mann–Whitney (p < 0.05). Bottom, The effect of adrenalectomy (ADX; n = 11) and corticosterone replacement (CORT/PW; n = 9) and sham surgery (SHAM; n = 10) on the mean number of responses (saline infusions + time-out responses) on the active lever in each hour of the 3 hr tests for reinstatement. The_asterisk_ indicates a difference from SHAM and CORT/PW in the Footshock test condition; Mann–Whitney (p < 0.05).

Fig. 3.

Effect of

-Phe in adrenalectomized animals with corticosterone replacement (CORT/P; n_= 5) on the mean ± SEM total number of responses on the active lever (saline infusions + time-out responses) in 2 hr tests for reinstatement after No Footshock and_Footshock (intermittent footshock, 10 min; 0.5 mA; 0.5 sec on; mean off period of 40 sec; immediately before the start of the session). All animals were tested after pretreatment with vehicle and with

-Phe given intracerebroventricularly 40 min before the test in both the No Footshock and Footshock test conditions. The number of responses in Footshock tests was greater than that in the No Footshock tests with both vehicle and

-Phe (Wilcoxon,p < 0.05). The asterisk indicates a difference from vehicle in the Footshock test condition (Wilcoxon, p < 0.05).

References

1. Ahmed SH, Koob GF. Cocaine- but not food-seeking behavior is reinstated by stress after extinction. Psychopharmacology (Berl) 1997;132:289–295. - PubMed
1. Ahmed S, Epping-Jordan M, Griffin P, Markou S, Heinrick S, De Souza E, Rivier J, Koob G. Maintenance of cocaine self-administration is not affected by pharmacological blockade of brain CRF receptors. Soc Neurosci Abstr. 1996;22:925.
1. Buckingham JC, Cooper TA. Differences in hypothalamic-pituitary-adrenocortical activity in the rat after acute and prolonged treatment with morphine. Neuroendocrinology. 1984;38:411–417. - PubMed
1. Cador M, Cole BJ, Koob GF, Stinus L, Le Moal M. Central administration of corticotropin releasing factor induces long-term sensitization to d-amphetamine. Brain Res. 1993;606:181–186. - PubMed
1. Chen Y, Mansbach R, Winter S, Brooks E, Collins J, Corman M, Dunaiskis A, Faraci S, Gallaschum J, Schmidt A, Schulz D. Synthesis and oral efficacy of a 4-(butylethylamino)pyrrolo[2,3-d]pyrimidine: a centrally active corticotropin-releasing factor 1 receptor antagonist. J Med Chem. 1997;40:1749–1754. - PubMed

The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats - PubMed (original) (raw)