The effects of passive and active administration of heroin, and associated conditioned stimuli, on consolidation of object memory

Abstract

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.

Modulation of memory consolidation by heroin and heroin conditioned stimuli: roles of expectation and dopamine D1 receptor?

“…Thus, rats able self-administer heroin displayed enhanced object location memory when assessed 72 hours after post-sample exposure to the 1 st (Fig 4A ), but not 6 th (Fig 4B ), session of self-administration. This nding, which incidentally replicates the observation that heroin self-administration in well-trained animals does not modulate consolidation of object memory (Francis et al, 2022), supports the idea that as the effects of heroin become anticipated, the experience of drug self-administration loses its ability to modulate memory. This said, it could be asked whether the larger amount of heroin consumed in later sessions (average intake on 1st session = 0.59 mg/kg; 6th session = 1.3 mg/kg) could explain the absence of memory modulation in well-trained animals.…”

“…Similarly, 0.10 mg/kg SCH prevented memory modulation induced by a change in schedule of selfadministered heroin in Study 2 (Fig 4C). It is unlikely that this latter effect was due to diminished heroin intake caused by a SCH-induced reduction in lever pressing (Fig 3C) because intake on this session (0.25 mg/kg) is within the range of heroin doses found to modulate object memory when injected postsample (Francis et al, 2022;Wolter et al, 2020). Interestingly, 0.10 mg/kg SCH also blocked modulation of memory by exposure to the heroin CS (operant chamber) in the absence of heroin (Fig 2C ), and this may be the rst evidence of involvement of the D1 receptor in conditioned memory modulation.…”

“…Heroin (Diacetylmorphine hydrochloride, Toronto Research Chemicals, Toronto, ON) and SCH23390 (Sigma-Aldrich, Oakville, ON) were dissolved in 0.9% physiological saline. For Study 1, heroin was injected at 1 mg/kg because this dose can enhance object location memory (Francis et al, 2022). For Study 2, heroin was self-administered IV at 0.05 mg/kg/infusion and a volume of 150 µl/infusion because of previous self-administration studies in our laboratory (Cummins & Leri, 2008;Leri & Stewart, 2001, 2002 .…”

“…Introduction White and Milner (1992) proposed that reinforcing stimuli promote the acquisition and maintenance of new behaviours by enhancing memory consolidation: a time-dependent process of memory stabilization that is central to learning (McGaugh, 2000). In support of this theory, there is signi cant evidence that chemical reinforcers such as morphine/heroin, cocaine, nicotine, as well as environmental stimuli associated with their effects (conditioned stimuli; CS), enhance memory consolidation in various tasks and species (Francis et al, 2022;Iñiguez et al, 2012;Wolter et al, 2019Wolter et al, , 2020. These observations are considered critical to addictive behaviours because drugs that enhance the consolidation of actions performed prior to, or during, drug intoxication have the potential to increase the probability that these actions will be repeated in the future (White, 1996).…”

“…These observations are considered critical to addictive behaviours because drugs that enhance the consolidation of actions performed prior to, or during, drug intoxication have the potential to increase the probability that these actions will be repeated in the future (White, 1996). Surprisingly, it has been recently observed that passive, but not self-administered, infusions of heroin enhanced consolidation of object location memory (Francis et al, 2022). This is puzzling because intravenous (IV) self-administration of drugs in animals is considered the gold standard for assessing their reinforcing e cacy and addictive potential (Thompson & Schuster, 1964; J.…”