2a:T546,

When given subcutaneously in gradually increasing doses, up to 1 mg/kg, NNC 756, a dopamine (DA) D-1 antagonist, failed to produce dystonia in eight drug-naive Cebus monkeys. In contrast, raclopride, a DA D-2 antagonist, produced dystonia at low doses (0.010-0.015 mg/kg). Following pre-treatment with raclopride, NNC 756 also induced dystonia at low doses (0.015-0.025 mg/kg), but continued treatment caused tolerance, and increasing doses of NNC 756 could be administered without induction of dystonia. NNC 756 induced a dose-dependent parkinsonism (slow, stiff movements and tremor), and more sedation than raclopride. After treatment for 14 weeks, withdrawal of raclopride (0.01 mg/kg) led to mild oral dyskinesia (tardive dyskinesia), while withdrawal of NNC 756 (1.0 mg/kg) led to a special grooming syndrome, but no dyskinesia. Withdrawal of raclopride as well as NNC 756 led to behavioural D-1 and D-2 dopamine supersensitivity in the form of increased dyskinesia (including grooming after NNC 756) induced by D-1 agonist (SKF 81297) and increased arousal induced by D-2 agonist (quinpirole). These results indicate that D-1 antagonists such as NNC 756 elicit fewer extrapyramidal symptoms (both acute and tardive) than D-2 antagonists such as raclopride, although extremely high doses may cause a special grooming withdrawal syndrome.

2b:T443,

The effects of the activation of adenosine receptors on core body temperature of mice have been studied in the present investigation. Intraperitoneal (i.p.) injection of non-selective adenosine agonists 5'-N ethyl- carboxamide adenosine (NECA; 0.001, 0.01 and 0.05 mg/kg), R-(N ⁶-phenylisopropyl)-adenosine (R-PIA; 0.01, 0.1 and 0.25 mg/kg) and selective A₁ adenosine agonist N⁶-cyclohexyladenosine (CHA; 0.1, 0.25 and 0.4 mg/kg) reduced core body temperature. However, R-PIA and CHA were less potent than NECA in reducing the core body temperature. Theophylline (12.5, 25 and 50 mg/kg) blocked the hypothermia of the adenosine agonists. Pre-treatment of animals with selective A₁ adenosine antagonist 8-phenyltheophylline (8-PT; 0.5, 1 and 2 mg/kg) decreased the hypothermic response of CHA but not of NECA and R-PIA. 8-PT potentiated the hypothermia induced by R-PIA. These results suggest that activation of both A₁ and A₂ adenosine receptors decreases core body temperature in mice.

2c:T4bf,

The current research methods, findings and questions that are being addressed in studies of the pharmacology of human memory and cognition are reviewed. Memory is not a unitary function. Neuropsychological studies of brain-damaged memory-impaired patients, as well as neuroimaging and drug studies in normal individuals indicate that different forms of learning and memory are subserved by different brain systems. Animal drug studies have also provided evidence that, while distinct, memory systems are not independent, but operate in close interaction with one another. Recent human studies of benzodiazepines and of cholinergic drugs demonstrate the value of the psychological models and of the experimental paradigms that are available from cognitive sciences for exploring how drugs alter cognitive and memory functions. They also show how drugs can be used as tools for analyzing the distinct neurochemical mechanisms underlying independent cognitive processes, and so find effective drugs rationally from a knowledge of the neurochemical bases of cognition. This research leads to specific recommendations concerning treatments that may improve memory functioning, for instance in Alzheimer's disease.

2d:T5f4,