Mode of administration (i.e., active vs passive) could influence the modulatory action that drugs of abuse exert on memory consolidation. Similarly, drug conditioned stimuli modulate memory consolidation and, therefore, acquisition and extinction of this conditioned response could also be influenced by mode of drug administration. Exploring these questions in male Sprague–Dawley rats, Study 1 assessed memory modulation by post-training 0, 0.3 and 1 mg/kg heroin injected subcutaneously in operant chambers (i.e., drug conditioned context). Study 2 asked a similar question but in rats trained to self-administer 0.05 mg/kg/infusion heroin intravenously, as well as in rats that received identical amounts of intravenous heroin but passively, using a yoked design. The period of heroin exposure was followed by repeated drug-free confinement in the conditioned context, and by sessions during which responses on the active lever had no scheduled consequences. Study 2 also included a cue-induced reinstatement session during which lever responses reactivated a light cue previously paired with intravenous heroin infusions. The post-training effects of injected/self-administered/yoked heroin, extinction and reinstatement sessions on memory consolidation were tested using the object location memory task. It was found that post-sample heroin enhanced memory in injected and yoked, but not self-administering, rats. However, post-sample exposure to the heroin cues (i.e., context or/and light cue) modulated memory equally in all groups. Taken together, these data support the conclusion that mode of administration impacts the cognitive consequences of exposure to drugs but not of environmental stimuli linked to their reinforcing effects.
It has been proposed that opiates modulate memory consolidation, but recent work has indicated that this effect may be mediated by how the drug is experienced (i.e., passive injections vs. self-administration). Because the dopamine (DA) D1 receptor is involved in processing of learning signals and attribution of salience to events experienced by an organism, two studies in male Sprague-Dawley rats tested the effect of blocking this receptor on modulation of memory consolidation by passive and self-administered heroin, in addition to conditioned memory modulation by heroin-paired cues. Using the object location memory task, Study 1 employed SCH23390 (0, 0.05, 0.10 mg/kg, SC) to modulate enhancement of memory consolidation induced by post-training injections of heroin (1 mg/kg, SC) as well as by exposure to the environment paired with heroin injections (6 pairings, 1 h each, 1 mg/kg). Study 2 was conducted in rats that could self-administer heroin (0.05 mg/kg/infusion, IV) and tested whether SCH23390 (0 and 0.1 mg/kg, SC) could prevent memory modulation induced by a change in schedule of self-administration (from fixed to variable ratio). It was found that while repeated passive injections of heroin retained their enhancing effect on memory, when self-administered, heroin enhanced consolidation of object location memory only at the beginning of self-administration and after a change in schedule. Importantly, SCH23390 blocked memory modulation by heroin when passively administered and when the drug was self-administered on a novel schedule. SCH23390 also blocked conditioned memory modulation induced by post-training exposure to heroin-paired cues. Taken together, these results suggest that modulation of memory consolidation by unconditioned and conditioned opiate reinforcers involve a D1-dependent mechanism of salience attribution linked to the anticipation of drug effects.
It has been theorized that drugs of abuse have enhancing effects on memory consolidation, but recent evidence suggests that this cognitive effect may be mediated by mode of drug administration (i.e., passive vs active). Hence, two studies were designed to test the hypothesis that modulation of memory consolidation by heroin, and by a heroin conditioned stimulus (CS), may be mediated by a dopamine D1 receptor dependent mechanism of prediction error. Using male Sprague-Dawley rats and the object location memory task, Study 1 employed the D1 antagonist SCH23390 (0, 0.05, 0.10 mg/kg, subcutaneous, SC) to modulate enhancement of memory consolidation induced by post-training passive injections of heroin (1 mg/kg, SC) as well as by exposure to the environment paired with heroin injections (6 pairings, 1 h each, 1 mg/kg). Study 2 investigated the same hypothesis but in animals that could learn to predict heroin because the drug was self-administered (0.05 mg/kg/infusion, intravenous), and further explored whether SCH23390 (0 and 0.1 mg/kg) could prevent memory modulation induced by a change in schedule of self-administration (from fixed to variable ratio). It was found that while repeated passive injections of heroin retained their modulatory effect on memory, when self-administered, heroin enhanced consolidation of object location only at the beginning of self-administration and after a change in schedule. Importantly, SCH23390 blocked memory modulation by heroin when passively administered and when the drug was self-administered on a novel schedule. SCH23390 also blocked conditioned memory modulation induced by post-training exposure to the heroin-paired CS. Taken together, these results suggest that modulation of memory consolidation by unconditioned and conditioned opiate reinforcers may involve a DA D1-dependent mechanism that could be encoding the anticipation of drug effects.
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