A brief, critical review of research on impaired control over alcohol use and suggestions for future studies.

Impaired control, defined as "a breakdown of an intention to limit consumption" (Heather et al. J Stud Alcohol 1993; 54, 701), has historically been considered an important aspect of addiction. Despite recognition of its importance to addiction and potential value as an early indicator of problem drinking risk, we argue that impaired control over alcohol use has not received sufficient research attention. In an effort to spark further research, the present critical review offers brief discussion of the current state of knowledge regarding impaired control and avenues for future research. Three main research areas are addressed: (i) epidemiology; (ii) measurement issues; and (iii) potential mechanisms underlying relationships between impaired control and subsequent problem drinking. Measurement issues include complexities involved in self-report assessment of impaired control, development and validation of human and animal laboratory models, and impaired control's relationship to other constructs (i.e., impulsivity and other difficulties with self-control; symptoms of dependence such as craving). We discuss briefly 2 potential mechanisms that may help to explain why some drinkers experience impaired control while others do not: neurobiological dysfunction and family history/genetics. Suggestions for future research are focused on ways in which the impaired control construct may enhance prediction of who might be at particular risk of subsequent problem drinking and to facilitate intervention to reduce problem alcohol use.

The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats.

The use of methamphetamine (MA) is increasing in the U.S. and elsewhere around the world. MA's capacity to cause addiction significantly exceeds other psychostimulant drugs, and its use negatively impacts learning and memory. Recently, attempts have been made to interfere with the presumed mechanism(s) underlying the establishment of drug-induced memory consolidation. The majority of these studies have employed matrix metalloproteinase (MMP) inhibitors to disrupt MMP-induced extracellular matrix molecule dependent synaptic reconfiguration, or GABA receptor agonists. The present investigation utilized an angiotensin IV (AngIV) analogue, Divalinal-AngIV (divalinal), to disrupt acquisition of MA-induced dependence in rats as measured using the conditioned place preference paradigm. Results indicate that both acute and chronic intracerebroventricular infusion of divalinal prior to each daily subcutaneous injection of MA prevented acquisition. However, divalinal was unable to prevent MA-induced reinstatement after prior acquisition followed by extinction trials. These results indicate that prevention of MA dependence can be accomplished by blockade of the brain AT4 receptor subtype. On the other hand, once MA-induced memory consolidation is in place divalinal appears to be ineffective. Mechanistic studies indicated that divalinal is a potent inhibitor of the hepatocyte growth factor (HGF)/c-Met receptor system, and thus it appears that a functional HGF/c-Met system is required for the acquisition of MA-mediated conditioned place preference.