ABSTRACT
The need to screen cerebroprotective compounds without anesthetic interference prompted the development of a model using hypoxic rats. In this model two outcome measures were used: (1) the time to reach isoelectric electroencephalogram (iEEG), caused by nitrogen gas inhalation in the test chamber, and (2) the time for behavioral recovery measuring the latency of restoration of the head-withdrawal reflex upon vibrissae stimulation. We report here data of blood chemistry, cerebral tissue oxygen measurements, a definition of a proposed scoring system, and the pharmacological results of RGH-2202. The findings with RGH-2202 are used here to show the utility of the screening method. Events during hypoxia: Arterial and venous pO(2), pCO(2), and pH, and brain tissue pO(2)significantly declined. Significant correlations were established among the pO(2)of cerebral tissue, blood, and the test chamber. RGH-2202 significantly and dose-dependently shortened the iEEG time; the compound's Effective Dose(30)was 227.8 mg kg(-1). Events during recovery: Immediately after the iEEG, when the atmosphere in the chamber was replaced with room air, the arterial, venous and brain tissue pO(2)increased above the control level and subsequently recovered to baseline levels. Behavioral recovery occurred before blood chemistry was otherwise normalized. RGH-2202 significantly and dose-dependently shortened the recovery time; the Effective Dose(30)was 8.71 mg kg(-1). The available data define and support the physiological basis of this practicable rat-screening model.
Subject(s)
Drug Evaluation, Preclinical/instrumentation , Drug Evaluation, Preclinical/methods , Neuroprotective Agents/administration & dosage , Thyrotropin-Releasing Hormone/analogs & derivatives , Administration, Oral , Animals , Brain/blood supply , Brain/drug effects , Brain/metabolism , Cerebrovascular Circulation/drug effects , Cerebrovascular Circulation/physiology , Disease Models, Animal , Electroencephalography/drug effects , Electroencephalography/instrumentation , Electroencephalography/methods , Hypoxia, Brain/blood , Hypoxia, Brain/chemically induced , Hypoxia, Brain/drug therapy , Male , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Rats , Rats, Wistar , Thyrotropin-Releasing Hormone/pharmacology , Thyrotropin-Releasing Hormone/therapeutic useABSTRACT
The authors examined the relationship of two dimensions of the theory of social development--vulnerability (predictors, risk factors) and protectivity--in two samples, schoolchildren aged ten to fifteen years and addictive drug users. On the basis of the Hirschi model of protective factors, they found that the most important protective factors (attachment, commitment, involvement, belief) act against substance use. A surprising finding was that among the predictors of the addicts some forms of escape from the family act against the development of drug use, that is, they can be regarded as a protective predictor. The findings of the study draw attention to the complexity of the vulnerability-protectivity relationship and to the need for further research.
Subject(s)
Family/psychology , Motivation , Personality Development , Substance-Related Disorders/psychology , Adolescent , Adult , Child , Child of Impaired Parents/psychology , Female , Humans , Hungary , Male , Risk Factors , Social Environment , Substance-Related Disorders/prevention & controlABSTRACT
Based on surveys and clinical data, it is concluded that the use of illegal drugs is spreading in Hungary. The social composition of drug users is changing and new forms of drugs and uses have appeared, such as heroin use and cocaine snorting. The legal regulation of access to drugs changed in 1993: stricter sentences can be imposed on drug traffickers, while the possibility has been created for drug users to undertake therapy in place of punishment. The Interministerial Committee on Drug Affairs and the Hungarian Association on Drug Use and Addiction have been set up. There are a few scientifically-based prevention programs. A number of clear paradigms have emerged in prevention policy and therapy, although it is not yet possible to see which of these will be confirmed by time and practice.
