Abstract
Previous studies employed a second-order schedule paradigm maintained by cocaine reinforcement to show that BP897, a dopamine D(3) partial agonist, selectively modulated drug-seeking behavior. We investigated its effect on drug-seeking behavior induced by presentation of stimuli associated with and predictive of cocaine availability after a period of extinction and in the absence of any further cocaine. Male rats were trained to associate discriminative stimuli (S(D)) with the availability of intravenous (i.v.) 0.25 mg/0.1 ml/infusion cocaine (S(D+)) or no-reward (S(D-)) saline solution. Each infusion of cocaine or saline was followed by a response-cue signaling 20-s time-out (TO). After meeting the self-administration training criterion rats were placed on extinction conditions during which i.v. solutions and S(D)s were withheld. Every other 3 days on which rats met the extinction criterion, reinstatement tests were conducted, presenting the S(D+) or S(D-) noncontingently together with a contingent presentation of cocaine- or saline-cues signaling 20-s TO. Regardless of the order of presentation or the nature of the stimuli (auditory or visual), cocaine-associated but not saline-associated stimuli reinstated responding on the previously active lever. Presentation of cocaine-associated stimuli induced lasting drug-seeking behavior for at least eight test sessions. BP897 (1.0 mg/kg i.p.) significantly attenuated this behavior. Since it has been reported that BP897 can interact with a panel of different receptors with high affinity, we evaluated the effects of 7-OH-DPAT, an agonist to D(3) receptors, raclopride, a preferential antagonist to D(2) receptors, and WAY 100,635, an antagonist at 5-HT(1A) receptors, on drug-seeking behavior. 7-OH-DPAT (0.1-3.0 mg/kg i.p.) had biphasic effects on reinstatement induced by the cocaine-associated cues, low dosages reducing and high dosages increasing the impact of cocaine-associated stimuli on rats' behavior. Raclopride (0.1, 0.3 mg/kg s.c.) completely prevented drug-seeking behavior induced by the reintroduction of cocaine-associated stimuli. WAY 100,635 (0.1-1.0 mg/kg s.c.) had no effect on this behavior. These results, while confirming that the partial agonist at the D(3) receptors, BP897, might be a useful medication, also suggest a role of D(2) receptors in cue-induced cocaine-seeking behavior.
| Original language | English |
|---|---|
| Pages (from-to) | 1150-1159 |
| Number of pages | 10 |
| Journal | Neuropsychopharmacology |
| Volume | 28 |
| Issue number | 6 |
| Publication status | Published - Jun 2003 |
Fingerprint
ASJC Scopus subject areas
- Pharmacology
Cite this
Cocaine-seeking behavior in response to drug-associated stimuli in rats : involvement of D3 and D2 dopamine receptors. / Cervo, L.; Carnovali, F.; Stark, J. A.; Mennini, T.
In: Neuropsychopharmacology, Vol. 28, No. 6, 06.2003, p. 1150-1159.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cocaine-seeking behavior in response to drug-associated stimuli in rats
T2 - involvement of D3 and D2 dopamine receptors.
AU - Cervo, L.
AU - Carnovali, F.
AU - Stark, J. A.
AU - Mennini, T.
PY - 2003/6
Y1 - 2003/6
N2 - Previous studies employed a second-order schedule paradigm maintained by cocaine reinforcement to show that BP897, a dopamine D(3) partial agonist, selectively modulated drug-seeking behavior. We investigated its effect on drug-seeking behavior induced by presentation of stimuli associated with and predictive of cocaine availability after a period of extinction and in the absence of any further cocaine. Male rats were trained to associate discriminative stimuli (S(D)) with the availability of intravenous (i.v.) 0.25 mg/0.1 ml/infusion cocaine (S(D+)) or no-reward (S(D-)) saline solution. Each infusion of cocaine or saline was followed by a response-cue signaling 20-s time-out (TO). After meeting the self-administration training criterion rats were placed on extinction conditions during which i.v. solutions and S(D)s were withheld. Every other 3 days on which rats met the extinction criterion, reinstatement tests were conducted, presenting the S(D+) or S(D-) noncontingently together with a contingent presentation of cocaine- or saline-cues signaling 20-s TO. Regardless of the order of presentation or the nature of the stimuli (auditory or visual), cocaine-associated but not saline-associated stimuli reinstated responding on the previously active lever. Presentation of cocaine-associated stimuli induced lasting drug-seeking behavior for at least eight test sessions. BP897 (1.0 mg/kg i.p.) significantly attenuated this behavior. Since it has been reported that BP897 can interact with a panel of different receptors with high affinity, we evaluated the effects of 7-OH-DPAT, an agonist to D(3) receptors, raclopride, a preferential antagonist to D(2) receptors, and WAY 100,635, an antagonist at 5-HT(1A) receptors, on drug-seeking behavior. 7-OH-DPAT (0.1-3.0 mg/kg i.p.) had biphasic effects on reinstatement induced by the cocaine-associated cues, low dosages reducing and high dosages increasing the impact of cocaine-associated stimuli on rats' behavior. Raclopride (0.1, 0.3 mg/kg s.c.) completely prevented drug-seeking behavior induced by the reintroduction of cocaine-associated stimuli. WAY 100,635 (0.1-1.0 mg/kg s.c.) had no effect on this behavior. These results, while confirming that the partial agonist at the D(3) receptors, BP897, might be a useful medication, also suggest a role of D(2) receptors in cue-induced cocaine-seeking behavior.
AB - Previous studies employed a second-order schedule paradigm maintained by cocaine reinforcement to show that BP897, a dopamine D(3) partial agonist, selectively modulated drug-seeking behavior. We investigated its effect on drug-seeking behavior induced by presentation of stimuli associated with and predictive of cocaine availability after a period of extinction and in the absence of any further cocaine. Male rats were trained to associate discriminative stimuli (S(D)) with the availability of intravenous (i.v.) 0.25 mg/0.1 ml/infusion cocaine (S(D+)) or no-reward (S(D-)) saline solution. Each infusion of cocaine or saline was followed by a response-cue signaling 20-s time-out (TO). After meeting the self-administration training criterion rats were placed on extinction conditions during which i.v. solutions and S(D)s were withheld. Every other 3 days on which rats met the extinction criterion, reinstatement tests were conducted, presenting the S(D+) or S(D-) noncontingently together with a contingent presentation of cocaine- or saline-cues signaling 20-s TO. Regardless of the order of presentation or the nature of the stimuli (auditory or visual), cocaine-associated but not saline-associated stimuli reinstated responding on the previously active lever. Presentation of cocaine-associated stimuli induced lasting drug-seeking behavior for at least eight test sessions. BP897 (1.0 mg/kg i.p.) significantly attenuated this behavior. Since it has been reported that BP897 can interact with a panel of different receptors with high affinity, we evaluated the effects of 7-OH-DPAT, an agonist to D(3) receptors, raclopride, a preferential antagonist to D(2) receptors, and WAY 100,635, an antagonist at 5-HT(1A) receptors, on drug-seeking behavior. 7-OH-DPAT (0.1-3.0 mg/kg i.p.) had biphasic effects on reinstatement induced by the cocaine-associated cues, low dosages reducing and high dosages increasing the impact of cocaine-associated stimuli on rats' behavior. Raclopride (0.1, 0.3 mg/kg s.c.) completely prevented drug-seeking behavior induced by the reintroduction of cocaine-associated stimuli. WAY 100,635 (0.1-1.0 mg/kg s.c.) had no effect on this behavior. These results, while confirming that the partial agonist at the D(3) receptors, BP897, might be a useful medication, also suggest a role of D(2) receptors in cue-induced cocaine-seeking behavior.
UR - http://www.scopus.com/inward/record.url?scp=0042092510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042092510&partnerID=8YFLogxK
M3 - Article
C2 - 12700684
AN - SCOPUS:0042092510
VL - 28
SP - 1150
EP - 1159
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 6
ER -