A lack of supersensitivity to opioid receptor agonists following chronic spinal opioid receptor antagonist administration in the rat.
5)-; Ala(2)-MePhe(4)-Gly(5)-; Animals; D-Penicillamine (2; Dose-Response Relationship; Drug; Enkephalin; Enkephalins/*pharmacology; Male; Naltrexone/analogs & derivatives/pharmacology; Narcotic Antagonists/*pharmacology; Opioid/*drug effects; Rats; Receptors; Somatostatin/analogs & derivatives/pharmacology; Species Specificity; Spinal Cord/*drug effects; Sprague-Dawley
1. Male Sprague-Dawley rats were chronically tested with intrathecal (i.t.) receptor selective opioid antagonists to determine if antinociceptive supersensitivity developed to selective i.t. opioid receptor agonists. 2. A subcutaneously implanted osmotic minipump was used to deliver the mu-opioid receptor antagonist CTOP (0.3 nmol) or the delta-opioid receptor antagonist naltrindole (5.5 nmol) for 7 days. 3. Following a 24 hr washout period, rats received a single i.t. dose (ED50) of either DAMPGO (for CTOP-treated animals) or DPDPE (for naltrindole-treated animals) and the antinociceptive effects of the agents were tested on the tail-flick test. 4. Our findings revealed that chronic spinal treatment with selective opioid receptor antagonists did not induce an antinociceptive supersensitivity to selective opioid receptor agonists. 5. Perhaps this lack of supersensitivity is reflective of difficulties inherent to opioid receptor antagonists that do not possess negative intrinsic activity.
Keck B J; Stafinsky J L; Uram M; Crisp T
General pharmacology
1995
1995-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0306-3623(94)00154-f" target="_blank" rel="noreferrer noopener">10.1016/0306-3623(94)00154-f</a>
Blockade of cocaine-induced conditioned place preference: relevance to cocaine abuse therapeutics.
Animals; Calcium Channel Blockers/pharmacology/therapeutic use; Cocaine/*antagonists & inhibitors; Conditioning (Psychology)/*drug effects; Humans; Narcotic Antagonists/pharmacology; Serotonin Antagonists/pharmacology; Substance-Related Disorders/*drug therapy
Conditioned place preference/aversion testing is a behavioral method believed capable of measuring the affective (positive, neutral or negative) properties of psychoactive drugs. Cocaine injections in rats reliably produces a positive place preference. Drugs that attenuate or block this effect of cocaine have obvious potential for developing treatments to address cocaine addiction as well as to add to the scientific understanding of the mechanism of cocaine's action at the cellular level. To date, six drugs have been reported to block the expression of a cocaine-induced conditioned place preference (CPP) and this review evidences the cocaine-induced CPP blockage by the two potent L-type calcium channel blockers, isradipine and nifedipine, the two serotonin-3 receptor antagonists, MDL72222 and ICS205-930, the delta opioid receptor selective antagonist naltrindole, and lastly, a mixed opioid agonist-antagonist buprenorphine. Additional evidence relating to the blockade of other cocaine behavioral effects by these putative blockers is addressed, where appropriate, from studies employing other procedures such as drug stimulus discrimination, self-administration, electrical brain stimulation and increases in locomotor activity. The significance of these findings is discussed in the context of their relevance to the development of treatment regimens to allow for cessation of cocaine abuse.
Calcagnetti D J; Keck B J; Quatrella L A; Schechter M D
Life sciences
1995
1905-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0024-3205(94)00414-n" target="_blank" rel="noreferrer noopener">10.1016/0024-3205(94)00414-n</a>