Dopamine‐dependent responses to cocaine depend on corticotropin‐releasing factor receptor subtypes

Abstract

The effects on locomotor response to cocaine challenge, acquisition of cocaine conditioned place preference and cocaine-induced dopamine (DA) release in nucleus accumbens and ventral tegmental area by the non-specific corticotropin-releasing factor (CRF) receptors antagonist a-helical CRF, the selective CRF receptor subtype 1 antagonist CP-154,526 and the selective CRF receptor subtype 2 antagonist anti-sauvagine-30 (AS-30) were investigated in rats. Both a-helical CRF (10 lg, i.c.v.) and 526 (3 lg, i.c.v.) decreased the cocaine-induced distance travelled, whereas AS-30 (3 lg, i.c.v.) did not show such an effect. The CRF receptor antagonists also have significant effects on stereotype counts induced by cocaine injection, in which the a-helical CRF or CP-154,526 but not AS-30 did significantly reduce the stereotype counts. a-Helical CRF (10 lg) prior to each injection of cocaine blocked cocaine conditioned place preference with no significant difference observed in the time spent in the drug-paired side between post-and pre-training and both 1 and 3 lg CP-154,526 also had significant inhibitory effects on cocaine-induced place preference. However, pretreatment with an i.c.v. infusion of AS-30 (1 or 3 lg) prior to each injection of cocaine did not affect the acquisition of conditioned place preference. The a-helical CRF and CP-154,526 reduced extracellular DA levels of nucleus accumbens and ventral tegmental area in response to the injection of cocaine. However, both a-helical CRF and CP-154,526 did not modify extracellular DA levels under basal conditions. In contrast, the i.c.v. infusion of AS-30 had no effects on either the basal DA or the cocaine-induced increase in DA release in nucleus accumbens and ventral tegmental area. These findings demonstrate that activation of the CRF receptor is involved in behavioral and neurochemical effects of cocaine challenge and cocaine reward and that the role of CRF receptor subtypes 1 and 2 in cocaine-induced locomotion, reward and DA release is not identical. The CRF receptor subtype 1 is largely responsible for the action of the CRF system on cocaine locomotion and reward. These results suggest that the CRF receptor antagonist, particularly the CRF receptor subtype 1 antagonist, might be of some value in the treatment of cocaine addiction and cocaine-related behavioral disorders.

Buprenorphine and a CRF1 Antagonist Block the Acquisition of Opiate Withdrawal-Induced Conditioned Place Aversion in Rats

“…The present study showing a blockade of the acquisition of place aversion produced by precipitated opiate withdrawal by a selective CRF 1 antagonist demonstrates that the effects of CRF antagonists extend to the motivational effects of opiate withdrawal, and that CRF might contribute to the development of opiate dependence in addition to mediating specific aspects of stress-induced modulation of opiate dependence. Antalarmin had no effect of its own in producing place conditioning, an observation consistent with the lack of a place preference with CP-154,526, a structurally similar CRF 1 antagonist (Lu et al, 2003). It is unknown whether a CRF antagonist would block the expression of opiate withdrawalinduced place aversion, and expression of withdrawal might involve memory as well as motivational components.…”

CRF receptors in the nucleus accumbens modulate partner preference in prairie voles

“…Thus, CRF receptor activation likely contributes to a larger circuit which converges in the NAcc to produce this complex social behavior. Consistent with this hypothesis, there is evidence that CRF receptors in the NAcc can modulate dopamine release into the striatum (Lu, Liu, Huang, and Zhang, 2003), and recent preliminary evidence suggesting that NAcc CRF receptor activation can stimulate bar pressing for natural reinforcement (Berridge, Pecine, and Schulkin, 2004). Another study has shown that CRF 2 receptors in the ventral tegmental area, which sends dopaminergic projections to NAcc, can induce long-term potentiation, a physiologic correlate of behavioral learning and reward association (Ungless, Singh, Crowder, Yaka, Ron, and Bonci, 2003).…”

Making a bad thing worse: adverse effects of stress on drug addiction

“…(122) Studies using CRFR1 antagonists demonstrate their involvement in the initial behavioral and biochemical effects of cocaine. For example, pharmacological blockade of CRFR1 inhibits cocaineinduced dopamine release (54) as well as reductions in the rewarding properties of cocaine (54) and locomotor activating effects (54,55). These studies point to a role of CRF in modulating the initial effects of addictive drugs, but more studies are needed to fully determine the role of CRF in the development of drug addiction.…”