True and False Concerns About Neuroenhancement: A Response to ‘Neuroenhancers, Addiction and Research Ethics’, by D M Shaw.

True and false concerns about neuroenhancement: a response to ‘Neuroenhancers, addiction and research ethics’, by D M Shaw.

J Med Ethics. 2013 Mar 6;
Heinz A, Kipke R, Müller S, Wiesing U

In his critical comment on our paper in this journal, Shaw argues that ‘false assumptions’ which we have criticised are in fact correct (‘Neuroenhancers, addiction and research ethics’). He suggests that the risk of addiction to neuroenhancers may not be relevant, and that safety and research in regard to neuroenhancement do not pose unique ethical problems. Here, we demonstrate that Shaw ignores key empirical research results, trivialises addiction, commits logical errors, confuses addictions and passions, argues on a speculative basis, and fails to distinguish the specific ethical conditions of clinical research from those relevant for research in healthy volunteers. Therefore, Shaw’s criticism cannot convince. HubMed – addiction

Noradrenergic Synaptic Function in the Bed Nucleus of the Stria Terminalis Varies in Animal Models of Anxiety and Addiction.

Neuropsychopharmacology. 2013 Mar 6;
McElligott ZA, Fox ME, Walsh PL, Urban DJ, Ferrel MS, Roth BL, Wightman RM

Lewis rats show increased anxiety-like behaviors and drug consumption compared to Sprague-Dawley rats. Prior work suggests norepinephrine (NE) signaling in the bed nucleus of the stria terminalis (BNST) could play a role in mediating these phenotypes. Here we investigated NE content and dynamics in the ventral BNST (vBNST) using fast-scan cyclic voltammetry in these two rat strains. We found that NE release evoked by electrical stimulus and its subsequent uptake was dysregulated in the more anxious Lewis rats. Because addiction is a multifaceted disease influenced by both genetic and environmental factors, we hypothesized NE dynamics would vary in these strains after the induction of a physical dependence on morphine. Following naloxone-precipitated morphine withdrawal, NE release and uptake dynamics were not changed in Lewis rats but were significantly altered in Sprague-Dawley rats. The alterations in Sprague-Dawley rats were accompanied by an increase in anxiety-like behavior in those animals as measured with the elevated plus maze. These studies suggest novel mechanisms involved in the development of affective disorders, and highlight the noradrenergic system in the vBNST as a common substrate for the manifestation of pathological anxiety and addiction.Neuropsychopharmacology accepted article preview online, 6 March 2013; doi:10.1038/npp.2013.63. HubMed – addiction

Effects of CCK-8 on the reinstatement of morphine-induced CPP and expression of behavioral sensitization in rats.

Neuroscience. 2013 Mar 2;
Wen D, Zang G, Sun D, Yang S, Yu F, Li S, Ma C, Cong B

Cholecystokinin octapeptide (CCK-8), a neuropeptide, plays an important role in morphine dependence and several addictive behaviors. We have previously reported that CCK-8 attenuates the acquisition of morphine-induced conditioned place preference (CPP), but the possible functions of CCK-8 on drug relapse remain unclear. Here we evaluated the effects of CCK-8 on the reinstatement of extinguished morphine-induced CPP and behavioral sensitization. A single intracerebroventricular injection of 0.1 and 1 ?g CCK-8 significantly attenuated both drug- (morphine) and stress- (foot shock) primed reinstatement of CPP and reduced the escalated locomotor activity in reinstatement tests. Additionally, CCK-8 blocked the expression of morphine-induced behavioral sensitization. However, administration of CCK-8 (0.01, 0.1 and 1 ?g) alone to morphine-pretreated rats could not trigger reinstatement of CPP and had no significant effect on threshold sensitivity to foot shock. In conclusion, our study identifies a distinct inhibitory effect of CCK-8 on the reinstatement of drug seeking behavior and provides a potential application to the medication of drug relapse. HubMed – addiction

mTOR activation is required for the anti-alcohol effect of ketamine, but not memantine, in alcohol-preferring rats.

Behav Brain Res. 2013 Mar 4;
Sabino V, Narayan AR, Zeric T, Steardo L, Cottone P

Glutamate NMDA receptors mediate many molecular and behavioral effects of alcohol, and they play a key role in the development of excessive drinking. Uncompetitive NMDA receptor antagonists may, therefore, have therapeutic potential for alcoholism. The first aim was to compare the effects of the NMDA antagonists memantine and ketamine on ethanol and saccharin drinking in alcohol-preferring rats. The second aim was to determine whether the effects of the two NMDA receptor antagonists were mediated by the mammalian target of rapamycin (mTOR). TSRI Sardinian alcohol-preferring rats were allowed to self-administer either 10% w/v ethanol or 0.08% w/v saccharin, and water. Operant responding and motor activity were assessed following administration of either memantine (0-10mg/kg) or ketamine (0-20mg/kg). Finally, ethanol self-administration was assessed in rats administered with either memantine or ketamine but pretreated with the mTOR inhibitor rapamycin (2.5mg/kg). The uncompetitive NMDA receptor antagonists memantine and ketamine dose-dependently reduced ethanol drinking in alcohol-preferring rats; while memantine had a preferential effect on alcohol over saccharin, ketamine reduced responding for both solutions. Neither antagonist induced malaise, as shown by the lack of effect on water intake and motor activity. The mTOR inhibitor rapamycin blocked the effects of ketamine, but not those of memantine. Memantine and ketamine both reduce alcohol drinking in alcohol-preferring rats, but only memantine is selective for alcohol. The effects of ketamine, but not memantine, are mediated by mTOR. The results support the therapeutic potential of uncompetitive NMDA receptor antagonists, especially memantine, in alcohol addiction. HubMed – addiction