The effects of morphine withdrawal and conditioned withdrawal on memory consolidation and c-Fos expression in the central amygdala.

The current study tested the hypothesis that drug withdrawal contributes to the addiction cycle in part because of an action on memory consolidation. Hence, four experiments in male Sprague-Dawley rats compared the effects of precipitated morphine withdrawal and conditioned morphine withdrawal on the consolidation of object memory and on activation of c-Fos in the central nucleus of the amygdala (CeA). It was found that immediate, but not 6 h delayed, post sample administration of 3 mg/kg of naltrexone significantly enhanced object memory in rats maintained, or previously maintained, on 10 mg/kg/day of morphine via osmotic minipumps. To establish whether conditioned withdrawal could also alter object memory, a contextual conditioning procedure was employed whereby morphine-maintained (10 mg/kg/day) animals received naltrexone (3 mg/kg) in a distinctive context (CS+) and vehicle in a separate context (CS-) for 10 days. During conditioning in the CS+, naltrexone suppressed locomotor activity, caused a rapid body weight loss and increased frequency of wet dog shakes. Interestingly, confinement to this CS+ immediately, but not 6 h, after the sample phase, also enhanced object memory. Finally, posttraining naltrexone and exposure to the CS+ both induced significant expression of c-Fos in the CeA. Therefore, this study reports for the first time that both acute precipitated withdrawal and conditioned withdrawal can facilitate memory consolidation, possibly through a common neural pathway that involves the central amygdala.

Double dissociation of perirhinal nicotinic acetylcholine receptors and dopamine D2 receptors in modulation of object memory consolidation by nicotine, cocaine and their conditioned stimuli.

There are indications that drug conditioned stimuli (CS) may activate neurochemical systems of memory modulation that are activated by the drugs themselves. To directly test this hypothesis, a cholinergic nicotinic receptor antagonist (mecamylamine; MEC: 0, 10 or 30 µg/side) and a dopamine D2 receptor antagonist (l-741,626: 0, 0.63, 2.5 µg/side) were infused in the perirhinal cortex (PRh) to block modulation of object recognition memory consolidation induced by 0.4 mg/kg nicotine, 20 mg/kg cocaine, or their CSs. To establish these CSs, male Sprague-Dawley rats were confined for 2 h in a chamber, the CS+, after injections of 0.4 mg/kg nicotine, or 20 mg/kg cocaine, and in another chamber, the CS-, after injections of vehicle. This was repeated over 10 days (5 drug/CS+ and 5 vehicle/CS- pairings in total). It was found that the memory enhancing action of post-sample nicotine was blocked by intra-PRh infusions of both MEC doses, and 30 µg/side MEC also blocked the memory enhancing action of the nicotine CS. Interestingly, intra-PRh MEC did not block the memory enhancing effect of cocaine, nor that of the cocaine CS. In contrast, the memory enhancing action of post-sample cocaine administration was blocked by both l-741,626 doses, and 2.5 µg/side also blocked the effect of the cocaine CS, but not the memory effects of nicotine or of the nicotine CS. This functional double dissociation strongly indicates that drug CSs modulate memory consolidation by activating neural systems that are activated by the drugs themselves.

Inhibition of noradrenergic and corticotrophin-releasing factor systems: Effects on enhancement of memory consolidation by unconditioned and conditioned heroin withdrawal.

The aim of the current study was to test the hypothesis that unconditioned and conditioned opioid withdrawal enhance memory consolidation through overlapping neural systems. The reported experiments focussed on noradrenaline (NA) and corticotrophin-releasing factor (CRF) because of their known involvement in both opioid withdrawal and memory consolidation. Male Sprague-Dawley rats were implanted with subcutaneous osmotic mini-pumps releasing 3.5 mg/kg/day heroin and received injections of 3 mg/kg naloxone (NLX) to precipitate withdrawal. NLX was preceded by 0.1-0.6 mg/kg lofexidine (LOF) (alpha-2 adrenergic agonist) or 10-20 mg/kg antalarmin (ANT) (CRF1 receptor antagonist), and all injections were administered immediately after (i.e., post-training method) the sample phase of the spontaneous object recognition memory task. The same procedure was repeated 7 days after removal of the mini-pumps. To establish conditioned withdrawal, heroin-exposed rats were confined for 2 h in a context (CS+) following injections of 3 mg/kg NLX and in another context (CS-) following vehicle injections. Seven days after removal of mini-pumps, the effects of immediate post-sample exposure to the CS+ (and CS-) preceded by 0.6 mg/kg LOF or 20 mg/kg ANT were assessed. It was found both LOF and ANT blocked the enhancement of object memory by post-sample NLX administration and by exposure to the CS+. These results suggest that pharmacological and psychological withdrawal impact memory storage by activating overlapping NA and CRF systems.

Extended amygdala, conditioned withdrawal and memory consolidation.

Opioid withdrawal can be associated to environmental cues through classical conditioning. Exposure to these cues can precipitate a state of conditioned withdrawal in abstinent subjects, and there are suggestions that conditioned withdrawal can perpetuate the addiction cycle in part by promoting the storage of memories. This review discusses evidence supporting the hypothesis that conditioned withdrawal facilitates memory consolidation by activating a neurocircuitry that involves the extended amygdala. Specifically, the central amygdala, the bed nucleus of the stria terminalis, and the nucleus accumbens shell interact functionally during withdrawal, mediate expression of conditioned responses, and are implicated in memory consolidation. From this perspective, the extended amygdala could be a neural pathway by which drug-seeking behaviour performed during a state of conditioned withdrawal is more likely to become habitual and persistent.

Memory enhancing effects of nicotine, cocaine, and their conditioned stimuli; effects of beta-adrenergic and dopamine D2 receptor antagonists.

BACKGROUND: There is evidence that post-training exposure to nicotine, cocaine, and their conditioned stimuli (CS), enhance memory consolidation in rats. The present study assessed the effects of blocking noradrenergic and dopaminergic receptors on nicotine and cocaine unconditioned and conditioned memory modulation. METHODS: Males Sprague-Dawley rats tested on the spontaneous object recognition task received post-sample exposure to 0.4 mg/kg nicotine, 20 mg/kg cocaine, or their CSs, in combination with 5-10 mg/kg propranolol (PRO; beta-adrenergic antagonist) or 0.2-0.6 mg/kg pimozide (PIM; dopamine D2 receptor antagonist). The CSs were established by confining rats in a chamber (the CS +) after injections of 0.4 mg/kg nicotine, or 20 mg/kg cocaine, for 2 h and in another chamber (the CS -) after injections of vehicle, repeated over 10 days (5 drug/CS + and 5 vehicle/CS - pairings in total). Object memory was tested 72 h post sample in drug-free animals. RESULTS: Co-administration of PRO or PIM blocked the memory-enhancing effects of post-training injections of nicotine, cocaine, and, importantly, exposure to their CSs. CONCLUSIONS: These data suggest that nicotine, cocaine as well as their conditioned stimuli share actions on overlapping noradrenergic and dopaminergic systems to modulate memory consolidation.

Opioid withdrawal and memory consolidation.

It is well established that learning and memory are central to substance dependence. This paper specifically reviews the effect of opioid withdrawal on memory consolidation. Although there is evidence that opioid withdrawal can interfere with initial acquisition and retrieval of older memories, there are several reasons to postulate a facilitatory action on the consolidation of newly acquired memories. In fact, there is substantial evidence that memory consolidation is facilitated by the release of stress hormones, that it requires the activation of the amygdala, of central noradrenergic and cholinergic pathways, and that it involves long-term potentiation. This review highlights evidence that very similar neurobiological processes are involved in opioid withdrawal, and summarizes recent results indicating that naltrexone-precipitated withdrawal enhanced consolidation in rats. From this neurocognitive perspective, therefore, opioid use may escalate during the addiction cycle in part because memories of stimuli and actions experienced during withdrawal are strengthened.

Modulation of object memory consolidation by heroin and heroin-conditioned stimuli: Role of opioid and noradrenergic systems.

There is recent evidence that cocaine, nicotine, and their conditioned stimuli have the ability to enhance memory consolidation. The present study compared the effects of post-training heroin and of a heroin contextual conditioned stimulus (CS+) on consolidation of object recognition memory and investigated the roles of opioid and beta-adrenergic receptors in heroin/CS+ memory modulation by co-administering the respective antagonists, naltrexone (NTX) and propranolol (PRO). Three experiments were performed in male Sprague-Dawley rats demonstrating that immediate, but not delayed, post-sample exposure to heroin (0.3, 1 mg/kg), or exposure (30 min) to a contextual CS+ paired with 1 mg/kg heroin (5 pairings, each 120 min), equally enhanced object memory. Importantly, while the memory enhancing effects of 1 mg/kg heroin and of the contextual CS+ were not altered by post-training co-administration of 3 mg/kg naltrexone, they were blocked by post-training co-administration of 10 mg/kg propranolol. Taken together, these data suggest that a context paired with heroin shares the memory enhancing effect of heroin itself and that these unconditioned and conditioned drug stimuli may modulate memory through the activation of beta-noradrenergic receptors.

Knowledge, attitude and practice of physiotherapists towards health promotion in Ghana.

BACKGROUND: Physiotherapists are well equipped to address health promotion issues with their patients and the public. However, no studies have been conducted in Ghana to assess the knowledge, attitude and practice of physiotherapists towards health promotion. OBJECTIVES: This study therefore seeks to determine the knowledge, attitude and practice of physiotherapists towards health promotion in Ghana. METHODS: This cross-sectional study was conducted at some selected physiotherapy departments in health facilities across Ghana. Ninety-one registered physiotherapists living and working in Ghana were recruited for this study. A closed-ended self-administered questionnaire was used to collect data on the demographics, knowledge, attitude and practice of physiotherapists towards health promotion. The scores for each section were calculated individually, and the final knowledge, attitude and practices score was obtained by calculating the total of the three sections. Statistical Package for Social Sciences version 22.0 was employed to analyse all the study variables. RESULTS: Physiotherapists' knowledge was 72%, attitude 84% and practice 87% towards health promotion. The association between the physiotherapists' knowledge of health promotion and practice was significant with Pearson's chi-square test (p = 0.013). But there was no significant association between knowledge and attitude of physiotherapists towards health promotion (p = 0.097). CONCLUSION: Physiotherapists have very good knowledge, attitude and practice towards health promotion in Ghana. This is essential for better integration into the scope of physiotherapy practice, and therefore, the health promotion policy in Ghana should be revised to include physiotherapists, because they are experts in exercise prescription and physical activity. CLINICAL IMPLICATIONS: The outcomes of this study could provide the impetus for physiotherapists to include health promotion in clinical and community services for primary prevention of non-communicable diseases as well as secondary and tertiary prevention of disability to promote functional independence.